| 1. |
- Aldridge, Jonathan, et al.
(author)
-
Blood PD-1+TFh and CTLA-4+CD4+ T cells predict remission after CTLA-4Ig treatment in early rheumatoid arthritis.
- 2022
-
In: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:3, s. 1233-1242
-
Journal article (peer-reviewed)abstract
- Treatment with CTLA-4Ig blocks T cell activation and is clinically effective in rheumatoid arthritis (RA). However, it is unknown if specific CD4+ T cell subsets in blood at baseline predict remission after CTLA-4Ig, or other biological treatments with different modes of action, and how treatment affects CD4+ T cells in patients with untreated early RA (eRA).This study included 60 patients with untreated eRA from a larger randomised trial. They were treated with methotrexate combined with CTLA-4Ig (abatacept, n=17), anti-IL6 receptor (tocilizumab, n=21) or anti-TNF (certolizumab-pegol, n=22). Disease activity was assessed by clinical disease activity index (CDAI), DAS28, swollen joint counts, tender joint counts, CRP and ESR. The primary outcome was CDAI remission (CDAI≤2.8) at week 24. Proportions of 12 CD4+ T cell subsets were measured by flow cytometry at baseline and after 4, 12 and 24weeks of treatment.In patients treated with CTLA-4Ig, the proportions of PD-1+TFh and CTLA-4+ conventional CD4+ T cells at baseline predicted CDAI remission at week 24. CD4+ T cell subset proportions could not predict remission after treatment with anti-IL6R or anti-TNF. The percentage of regulatory T cells (Tregs) expressing CTLA-4 decreased in all treatment arms by 24weeks, but only CTLA-4Ig treatment significantly reduced the proportions of Tregs and PD-1+T follicular helper (TFh) cells.These findings indicate that circulating proportions PD-1+TFh and CTLA-4+ conventional CD4+ T cells at baseline may serve as predictive biomarkers for remission in early RA after CTLA-4Ig treatment.
|
|
| 2. |
- Aldridge, Jonathan, et al.
(author)
-
T helper cells in synovial fluid of patients with rheumatoid arthritis primarily have a Th1 and a CXCR3(+)Th2 phenotype
- 2020
-
In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 22:1
-
Journal article (peer-reviewed)abstract
- Background The majority of CD4(+)T helper (Th) cells found in the synovial fluid (SF) of patients with rheumatoid arthritis (RA) express CXCR3, a receptor associated with Th1 cells. In blood, subsets of Th2 and Th17 cells also express CXCR3, but it is unknown if these cells are present in RA SF or how cytokines from these subsets affect cytokine/chemokine secretion by fibroblast-like synoviocytes (FLS) from patients with RA. Methods We examined the proportions of Th1, Th2, CXCR3(+)Th2, Th17, CXCR3(+)Th17, Th1Th17, peripheral T helper (TPh) and T follicular helper (TFh) cells in paired SF and blood, as well as the phenotype of TPh and TFh cells in RA SF (n = 8), by the use of flow cytometry. We also examined the cytokine/chemokine profile in paired SF and plasma (n = 8) and in culture supernatants of FLS from patients with chronic RA (n = 7) stimulated with Th-associated cytokines, by the use of cytometric bead arrays and ELISA. Cytokine receptor expression in FLS (n = 3) were assessed by the use of RNA sequencing and qPCR. Results The proportions of Th1 and CXCR3(+)Th2 cells were higher in SF than in blood (P < 0.05). TPh and PD-1(high)TFh in RA SF were primarily of a Th1 and a CXCR3(+)Th2 phenotype. Moreover, the levels of CXCL9, CXCL10, CCL20, CCL2, CXCL8, IL-6 and IL-10 were higher in SF than in plasma (P < 0.05). Lastly, IL-4, IL-13 and IL-17A induced RA FLS to secrete proinflammatory IL-6, CCL2, CXCL1 and CXCL8, while IFN gamma mainly induced CXCL10. Conclusion These findings indicate that not only Th1 but also CXCR3(+)Th2 cells may have a pathogenic role in RA synovial inflammation.
|
|
| 3. |
- Andersson, Jennie, 1978, et al.
(author)
-
Eosinophils from hematopoietic stem cell recipients suppress allogeneic T cell proliferation.
- 2014
-
In: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. - : Elsevier BV. - 1523-6536. ; 20:12, s. 1891-8
-
Journal article (peer-reviewed)abstract
- Eosinophilia has been associated with less severe graft-versus-host disease (GVHD), but the underlying mechanism is unknown. We hypothesized that eosinophils diminish allogeneic T cell activation in patients with chronic GVHD. The capacity of eosinophils derived from healthy subjects and hematopoietic stem cell (HSC) transplant recipients, with or without chronic GVHD, to reduce allogeneic T cell proliferation was evaluated using a mixed leukocyte reaction. Eosinophil-mediated inhibition of proliferation was observed for the eosinophils of both healthy subjects and patients who underwent HSC transplantation. Eosinophils from patients with and without chronic GVHD were equally suppressive. Healthy eosinophils required cell-to-cell contact for their suppressive capacity, which was directed against CD4(+) T cells and CD8(+) T cells. Neither eosinophilic cationic protein, eosinophil-derived neurotoxin, indoleamine 2,3-dioxygenase, or increased numbers of regulatory T cells could account for the suppressive effect of healthy eosinophils. Real-time quantitative PCR analysis revealed significantly increased mRNA levels of the immunoregulatory protein galectin-10 in the eosinophils of both chronic GVHD patients and patients without GVHD, as compared with those from healthy subjects. The upregulation of galectin-10 expression in eosinophils from patients suggests a stimulatory effect of HSC transplantation in itself on eosinophilic galectin-10 expression, regardless of chronic GVHD status. To conclude, eosinophils from HSC transplant recipients and healthy subjects have a T cell suppressive capacity.
|
|
| 4. |
- Andersson Lundell, Anna-Carin, 1976, et al.
(author)
-
Development of gut-homing receptors on circulating B cells during infancy.
- 2011
-
In: Clinical immunology. - : Elsevier BV. - 1521-7035 .- 1521-6616. ; 138:1, s. 97-106
-
Journal article (peer-reviewed)abstract
- B cell gut-homing is mainly mediated by α4β7, CCR9 and CCR10. We here studied the expression of these receptors on B cells from cord blood and from peripheral blood at 1, 4, 18 and 36months of age in a prospective cohort of Swedish infants. The proportion of all B cells expressing α4β7 as well as the fraction of CCR10+ B cells expressing α4β7 was highest in early infancy. Nearly all naïve B cells in all age groups expressed α4β7, whereas the expression on class-switched B cells decreased with age. Moreover, the proportion of both IgA+ and IgG+ B cells expressing α4β7, CCR9 and CCR10 were higher during the first months when compared to adults. In conclusion, the high fraction of circulating IgA+ and IgG+ B cells expressing CCR9 and CCR10 in the first months of life indicates activation of naïve B cells in the gut, coinciding with bacterial colonization.
|
|
| 5. |
- Hennings, Viktoria, et al.
(author)
-
The presence of serum anti-SARS-CoV-2 IgA appears to protect primary health care workers from COVID-19.
- 2022
-
In: European journal of immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 52:5, s. 800-809
-
Journal article (peer-reviewed)abstract
- The patterns of humoral and cellular responses to SARS-CoV-2 were studied in Swedish primary health care workers (n = 156) for 6 months during the Covid-19 pandemic. Serum IgA and IgG to SARS-CoV-2, T-cell proliferation and cytokine secretion, demographic and clinical data, PCR-verified infection, and self-reported symptoms were monitored. The multivariate method OPLS-DA was used to identify immune response patterns coupled to protection from Covid-19. Contracting Covid-19 was associated with SARS-CoV-2-specific neutralizing serum IgG, T cell, IFN-γ, and granzyme B responses to SARS-CoV-2, self-reported typical Covid-19 symptoms, male sex, higher BMI, and hypertension. Not contracting Covid-19 was associated with female sex, IgA-dominated, or no antibody responses to SARS-CoV-2, airborne allergy, and smoking. The IgG-responders had SARS-CoV-2-specific T-cell responses including a cytotoxic CD4+ T-cell population expressing CD25, CD38, CD69, CD194, CD279, CTLA-4, and granzyme B. IgA-responders with no IgG response to SARS-CoV-2 constituted 10% of the study population. The IgA responses were partially neutralizing and only seen in individuals who did not succumb to Covid-19. To conclude, serum IgG-dominated responses correlated with T-cell responses to SARS-CoV-2 and PCR-confirmed Covid-19, whereas IgA-dominated responses correlated with not contracting the infection.
|
|
| 6. |
- Hjälmeskog, Karin, 1954-, et al.
(author)
-
Didaktik i förskolan
- 2020
-
Book (other academic/artistic)abstract
- Att vara förskollärare är ett mångfacetterat och utmanande yrke som kräver kunnande inom en mängd olika områden. Det kräver också en helhetssyn på barnen där omsorg, utveckling och lärande hänger ihop. På förskolan läggs grunden för att barnen utvecklas och lär under resten av sina liv.I den här boken tas didaktik upp ur ett antal olika perspektiv. Det handlar om alla de didaktiska val förskolläraren gör, och om att se olika alternativ när man planerar och genomför undervisning. Det handlar också om att undersöka vad som sker i undervisningen, och att reflektera över det som skett och varför.I bokens olika kapitel diskuteras bland annat hur man som förskollärare kan stödja barns utveckling av ämneskunskap och hur man kan stödja barns kommunikativa förmåga, i tal och skrift. Omsorg, utveckling och lärande i vardagliga situationer i förskolan samt hur man utvecklar ett genusmedvetet förhållningssätt tas också upp.Med konkreta exempel hjälper boken blivande och verksamma förskollärare att konkretisera läroplanens mål. Förhoppningen är att både inspirera och utmana förskollärares tankar om sitt arbete, och bidra till givande diskussioner i arbetslaget.Bokens författare har tillsammans lång erfarenhet från förskola, forskning och undervisning på förskollärarprogram vid flera universitet. Bland annat verkar de nu vid Uppsala universitet och Kungliga tekniska högskolan.
|
|
| 7. |
- Lingblom, Christine, 1984, et al.
(author)
-
Regulatory Eosinophils Suppress T Cells Partly through Galectin-10
- 2017
-
In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 198:12, s. 4672-4681
-
Journal article (peer-reviewed)abstract
- Eosinophils have the capacity to regulate the function of T cell subsets. Our aim was to test the hypothesis of the existence of a regulatory subset of eosinophils. Human eosinophils were incubated with T cells that were stimulated with allogeneic leukocytes or CD3/ CD28 cross-linking. After 2 d of coculture, 11% of the eosinophils gained CD16 expression. A CD16(hi) subset of eosinophils, encompassing 1-5% of all eosinophils, was also identified in the blood of healthy subjects. FACS sorting showed that these CD16(hi) eosinophils were significantly stronger suppressors of T cell proliferation than were conventional CD16 neg eosinophils. Human eosinophils contain stores of the immunoregulatory protein galectin-10. We found that Ab-mediated neutralization of galectin-10 partially abrogated the suppressive function of the eosinophils. Moreover, recombinant galectin-10 by itself was able to suppress T cell proliferation. Finally, we detected galectin-10-containing immune synapses between eosinophils and lymphocytes. To conclude, we describe a subset of suppressive eosinophils expressing CD16 that may escape detection because CD16-based negative selection is the standard procedure for the isolation of human eosinophils. Moreover, we show that galectin-10 functions as a T cell-suppressive molecule in eosinophils.
|
|
| 8. |
- Strömbeck, Anna, et al.
(author)
-
Allergic disease in 8-year old children is preceded by delayed B-cell maturation.
- 2017
-
In: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 1365-2222. ; 47:7, s. 918-928
-
Journal article (peer-reviewed)abstract
- We previously reported that exposure to a farming environment is allergy-protective, while high proportions of neonatal immature/naïve CD5(+) B cells and putative regulatory T cells (Tregs) are risk factors for development of allergic disease and sensitization up to 3 years of age.To examine if B- and T-cell maturation are associated with allergic disease and farming environment over the first 8 years in life.In the prospective FARMFLORA study, including both farming and non-farming families, 48 out of 65 children took part in the 8-year follow-up study. Various B- and T-cell maturation variables were examined in blood samples obtained at several occasions from birth to 8 years of age and related to doctors' diagnosed allergic disease and sensitization, and to farming environment.We found that the incidence of allergic disease was lower among farmers' compared to non-farmers' children during the 8-years follow-up period, and that farmers' children had higher proportions of memory B cells at 8 years of age. Moreover, a high proportion of neonatal CD5(+) B cells was a risk factor for and may predict development of allergic disease at 8 years of age. A high proportion of Tregs was not protective against development of these conditions.High proportions of neonatal naïve B cells remained as a risk factor for allergic disease in school-aged children. Thus, the accelerated B-cell maturation observed among farmers' children may be crucial for the allergy-protective effect of a farming environment. This article is protected by copyright. All rights reserved.
|
|
| 9. |
- Vasileiadis, Georgios, et al.
(author)
-
Adipocytokines in Untreated Newly Diagnosed Rheumatoid Arthritis: Association with Circulating Chemokines and Markers of Inflammation
- 2021
-
In: Biomolecules. - : MDPI AG. - 2218-273X. ; 11:2
-
Journal article (peer-reviewed)abstract
- Adiponectin, leptin, and resistin are adipocytokines whose levels are elevated in blood and synovial fluid from patients with rheumatoid arthritis (RA). However, their role in RA pathogenesis is unclear. Here, we examined whether adipocytokines are associated with circulating chemokines, markers of inflammation and RA disease activity in patients with untreated newly diagnosed RA. Plasma levels of 15 chemokines, adiponectin, leptin, and resistin were measured using flow cytometry bead-based immunoassay or enzyme-linked immunosorbent assay (ELISA) in a cohort of 70 patients with untreated newly diagnosed RA. Markers of inflammation and disease activity were also assessed in all patients. Positive association was found between total adiponectin and CXCL10 (beta = 0.344, p = 0.021), CCL2 (beta = 0.342, p = 0.012), and CXCL9 (beta = 0.308, p = 0.044), whereas high-molecular weight (HMW) adiponectin associated only with CXCL9 (beta = 0.308, p = 0.033). Furthermore, both total and HMW adiponectin were associated with C-reactive protein (beta = 0.485, p = 0.001; beta = 0.463, p = 0.001) and erythrocyte sedimentation rate (beta = 0.442, p = 0.001; beta = 0.507, p < 0.001). Leptin and resistin were not associated with plasma chemokines, markers of inflammation, or disease activity scores. Our study shows an association between circulating adiponectin and pro-inflammatory chemokines involved in RA pathogenesis as well as markers of inflammation in a well-characterized cohort of patients with untreated newly diagnosed RA.
|
|
| 10. |
- Aldridge, Jonathan, et al.
(author)
-
Blood chemokine levels are markers of disease activity but not predictors of remission in early rheumatoid arthritis.
- 2022
-
In: Clinical and experimental rheumatology. - : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 40:7, s. 1393-1402
-
Journal article (peer-reviewed)abstract
- In early rheumatoid arthritis (eRA) plasma levels of specific chemokines have been shown to correlate with disease activity. However, it is unclear whether pre-treatment chemokine levels can predict disease remission at week 24, and it is not known how biological treatments with different modes of action affect plasma chemokine levels in patients with untreated eRA.This study included 347 Swedish patients with untreated eRA from the larger NORD-STAR randomised treatment trial. Here, eRA patients were treated with methotrexate combined with either prednisolone, anti-TNF (certolizumab-pegol), CTLA-4Ig (abatacept) or anti-IL6 receptor (tocilizumab). The primary clinical outcome was remission by clinical disease activity index (CDAI) defined as CDAI ≤ 2.8. Disease activity was assessed by CDAI, DAS28-ESR, DAS28-CRP, swollen joint counts, tender joint counts, ESR and CRP. The plasma concentrations of 14 chemokines were measured at baseline and after 24 weeks of treatment by bead-based immunoassay or ELISA.Baseline plasma concentrations of CXCL10, CXCL8, CXCL9, CXCL11, CXCL5 and CCL2 correlated with baseline disease activity measures. After 24 weeks of treatment, plasma levels of CXCL10, CXCL8, CXCL9, CXCL11 and CXCL13 decreased in all treatment groups except in patients treated with anti-IL6 receptor. In multivariate factor analysis, plasma chemokine levels at baseline could not differentiate patients who attained remission by week 24 from those who did not in any of the treatment groups.In patients with untreated eRA, plasma levels of several chemokines correlate with disease activity at baseline but cannot predict remission after 24 weeks of treatment with methotrexate combined with prednisolone, anti‑TNF, CTLA‑4Ig or anti‑IL6R.
|
|
| 11. |
- Aldridge, Jonathan, et al.
(author)
-
Sex-based differences in association between circulating T cell subsets and disease activity in untreated early rheumatoid arthritis patients
- 2018
-
In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 20:1
-
Journal article (peer-reviewed)abstract
- Background: It is not known if sex-based disparities in immunological factors contribute to the disease process in rheumatoid arthritis (RA). Hence, we examined whether circulating T cell subset proportions and their association with disease activity differed in male and female patients with untreated early rheumatoid arthritis (ueRA). Methods: Proportions of T cell subsets were analyzed in peripheral blood from 72 ueRA DMARD-and corticosteroid-naive patients (50 females and 22 males) and in 31 healthy age-and sex-matched controls. Broad analysis of helper and regulatory CD4(+) T cell subsets was done using flow cytometry. Disease activity in patients was assessed using DAS28, CDAI, swollen joint counts, tender joint counts, CRP, and ESR. Results: Multivariate factor analyses showed that male and female ueRA patients display distinct profiles of association between disease activity and circulating T cell subset proportions. In male, but not female, ueRA patients Th2 cells showed a positive association with disease activity and correlated significantly with DAS28-ESR, CDAI, and swollen and tender joint counts. Likewise, proportions of non-regulatory CTLA-4(+) T cells associated positively with disease activity in male patients only, and correlated with DAS28-ESR. In contrast, there was a negative relation between Th1Th17 subset proportions and disease activity in males only. The proportions of Th17 cells correlated positively with DAS28-ESR in males only, while proportions of Th1 cells showed no relation to disease activity in either sex. There were no significant differences in proportions of T cell subsets between the sexes in patients with ueRA. Conclusions: Our findings show sex-based differences in the association between T cell subsets and disease activity in ueRA patients, and that Th2 helper T cells may have a role in regulating disease activity in male patients.
|
|
| 12. |
- Andersson, Henrik, et al.
(author)
-
Assaying cardiac biomarkers for toxicity testing using biosensing and cardiomyocytes derived from human embryonic stem cells
- 2010
-
In: JOURNAL OF BIOTECHNOLOGY. - : Elsevier Science B.V., Amsterdam.. - 0168-1656 .- 1873-4863. ; 150:1, s. 175-181
-
Journal article (peer-reviewed)abstract
- Human embryonic stem cell (hESC) derived cardiomyocytes are in the present study being used for testing drug-induced cardiotoxicity in a biosensor set-up. The design of an in vitro testing alternative provides a novel opportunity to surpass previous methods based on rodent cells or cell lines due to its significantly higher toxicological relevance. In this report we demonstrate how hESC-derived cardiomyocytes release detectable levels of two clinically decisive cardiac biomarkers, cardiac troponin T and fatty acid binding protein 3, when the cardiac cells are exposed to the well-known cardioactive drug compound. doxorubicin. The release is monitored by the immuno-biosensor technique surface plasmon resonance, particularly appropriate due to its capacity for parallel and high-throughput analysis in complex media.
|
|
| 13. |
- Johansson, Sofi, 1975, et al.
(author)
-
CC16 Inhibits the Migration of Eosinophils Towards the Formyl Peptide fMLF but not Towards PGD(2).
- 2009
-
In: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 32:2, s. 65-9
-
Journal article (peer-reviewed)abstract
- Clara cell 16-kDa (CC16) is an anti-inflammatory protein chiefly produced in the lung epithelium. CC16 has been shown to inhibit the migration of rabbit neutrophils and human monocytes toward the formyl peptide N-formyl-methionine-leucin-phenylalanin (fMLF). Eosinophils migrate towards prostaglandin D2 (PGD(2)) and CC16 has been shown to bind to PGD(2). Therefore we investigated if CC16 could inhibit the migration of human eosinophils and neutrophils towards fMLF and/or PGD(2). Migration of eosinophils and neutrophils was assessed in a microplate migration system using specific ligands and receptor antagonists. CC16 inhibited the migration of eosinophils and neutrophils toward fMLF, which is likely to result from the interaction of CC16 with members of the formyl-peptide receptor family. However, CC16 did not inhibit eosinophil migration towards PGD(2). We therefore propose that CC16 may down-modulate the entry of human eosinophils and neutrophils into the airways during inflammation in the lung.
|
|
| 14. |
- Karlsson, Johanna, 1973, et al.
(author)
-
Pneumococcal vaccine responses in elderly patients with multiple myeloma, Waldenstrom’s macroglobulinemia, and monoclonal gammopathy of undetermined significance
- 2013
-
In: Trials in vaccinology. - : Elsevier BV. - 1879-4378. ; 2, s. 31-38
-
Journal article (peer-reviewed)abstract
- Background Vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPV) has been recommended for elderly patients with B cell malignancies and dysfunctions because of their enhanced susceptibility to pneumococcal infections. More recent recommendations advocate the use of conjugate pneumococcal vaccines. Methods We compared responses to single dose vaccination with either PPV or the 7-valent pneumococcal conjugate vaccine (PCV7) in fifty-six patients ⩾60 years with a diagnosis of multiple myeloma (n = 24), Waldenstrom’s macroglobulinemia (n = 15) and the non-malignant B cell disorder monoclonal gammopathy of undetermined significance (MGUS) (n = 17), and 20 age-matched controls. Serum was collected prior to vaccination and 4–8 weeks later, and analyzed for IgG antibody levels to pneumococcal serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F by ELISA. Functional antibody activity towards pneumococcal serotypes 4 and 14 was measured using an opsonophagocytic killing assay (OPA). Results All patient groups had lower pre-vaccination IgG antibody and OPA titers to the investigated serotypes compared to the healthy controls. Following vaccination, myeloma patients responded with significant IgG titer increases to 1/7 serotypes and OPA titer increases to 1/2 serotypes. Corresponding IgG and OPA vaccine responses were 3/7 and 0/2 for Waldenstrom patients, 4/7 and 1/2 for MGUS patients, and 4/7 and 2/2 for the healthy controls, respectively. Notably high antibody levels without corresponding OPA titers were seen among a few myeloma patients indicating the presence of non-functional antibodies. Neither of the two vaccines elicited significantly higher serotype-specific IgG concentrations, OPA titers or antibody fold increases in any of the study groups. Hypogammaglobulinemia and ongoing chemotherapy were associated with poor vaccine responses in a multivariate analysis. Conclusion Our findings confirm that B cell malignancies and disorders among elderly patients are associated with suboptimal responses to pneumococcal vaccination. Single-dose PCV7 was not shown to be superior to PPV.
|
|
| 15. |
- Li, Lizhen, 1977, et al.
(author)
-
Protective role of reactive astrocytes in brain ischemia.
- 2008
-
In: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 28:3, s. 468-81
-
Journal article (peer-reviewed)abstract
- Reactive astrocytes are thought to protect the penumbra during brain ischemia, but direct evidence has been lacking due to the absence of suitable experimental models. Previously, we generated mice deficient in two intermediate filament (IF) proteins, glial fibrillary acidic protein (GFAP) and vimentin, whose upregulation is the hallmark of reactive astrocytes. GFAP(-/-)Vim(-/-) mice exhibit attenuated posttraumatic reactive gliosis, improved integration of neural grafts, and posttraumatic regeneration. Seven days after middle cerebral artery (MCA) transection, infarct volume was 210 to 350% higher in GFAP(-/-)Vim(-/-) than in wild-type (WT) mice; GFAP(-/-), Vim(-/-) and WT mice had the same infarct volume. Endothelin B receptor (ET(B)R) immunoreactivity was strong on cultured astrocytes and reactive astrocytes around infarct in WT mice but undetectable in GFAP(-/-)Vim(-/-) astrocytes. In WT astrocytes, ET(B)R colocalized extensively with bundles of IFs. GFAP(-/-)Vim(-/-) astrocytes showed attenuated endothelin-3-induced blockage of gap junctions. Total and glutamate transporter-1 (GLT-1)-mediated glutamate transport was lower in GFAP(-/-)Vim(-/-) than in WT mice. DNA array analysis and quantitative real-time PCR showed downregulation of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of tissue plasminogen activator. Thus, reactive astrocytes have a protective role in brain ischemia, and the absence of astrocyte IFs is linked to changes in glutamate transport, ET(B)R-mediated control of gap junctions, and PAI-1 expression.
|
|
| 16. |
- Lindahl, Olof A, et al.
(author)
-
Biomedical engineering research improves the health care industry
- 2014
-
In: XIII Mediterranean Conference on Medical and Biological Engineering and Computing 2013. - Cham : Springer. - 9783319008455 - 9783319008462 ; , s. 1124-1126
-
Conference paper (peer-reviewed)abstract
- The health care industry is dependent on new innovations for its survival and expansion. Health care innovations are also important for improving patient care. Through activities at the centre for biomedical engineering and physics (CMTF) we have generated growth both in academia at the universities and in the industry in northern Sweden. Fruitful cooperation was generated between 26 research projects and about 15 established companies in the field of biomedical engineering. The established researcher-owned company for business development of the research results from the CMTF, CMTF Business Development Co Ltd, has so far launched three spin-off companies and has 10 new business leads to develop. The activities have also increased the interest for commercialization and entrepreneurship among the scientists in the centre. So far a total of nine spin-off companies have resulted from the CMTF-research since the year 2000 that has improved the health care market in northern Sweden. © Springer International Publishing Switzerland 2014.
|
|
| 17. |
|
|
| 18. |
- Lindahl, Olof, et al.
(author)
-
From biomedical research to spin-off companies for the health care market
- 2010
-
In: The XII Mediterranean Conference on Medical and Biological Engineering and Computing. - Berlin, Heidelberg : Springer. ; , s. 624-626, s. 624-626
-
Conference paper (peer-reviewed)abstract
- Through research at the centre for biomedical engineering and physics (CMTF) seven new companies have been established in Northern Sweden. The activities have generated growth both in academia at the universities and in the industry in Northern Sweden. Cooperation was built up between the 23 research projects and more than 20 established companies in the field of biomedical engineering. A researcher-owned company for business development of the research results from the CMTF has been established, CMTF Business Development Co Ltd, and has launched its first spin-off company in the autumn 2009. It has also increased the interest for commercial and entrepreneurship questions among the scientists in the centre. So far seven spin-off companies have resulted from the CMTF-research.
|
|
| 19. |
|
|
| 20. |
- Lingblom, Christine, 1984, et al.
(author)
-
Kinetic studies of galectin-10 release from eosinophils exposed to proliferating T cells
- 2021
-
In: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 203:2, s. 230-234
-
Journal article (peer-reviewed)abstract
- Galectin-10 is involved in the T cell suppressive activity of regulatory T cells and eosinophils alike. We have identified a subpopulation of T cell suppressive eosinophils that express CD16 on the surface and contain more galectin-10 compared with conventional CD16-negative eosinophils. Our main goal was to determine how the intracellular protein galectin-10 is released from eosinophils when exposed to proliferating T cells and if such release could be inhibited. Confocal microscopy and imaging flow cytometry were used to study the release of galectin-10 from eosinophils incubated with polyclonally activated T cells. T cell proliferation was monitored by measurement of the incorporation of [H-3]-thymidine. Initially, galectin-10-containing synapses formed between eosinophils and T cells. Subsequently, the plasma membrane of eosinophils began to disintegrate and cap-like accumulations of galectin-10 budded on the eosinophil cell surface. Lastly, eosinophil extracellular traps composed of nuclear DNA and galectin-10 were freed. It was solely the CD16-expressing suppressive eosinophils that formed synapses and eosinophil extracellular traps containing galectin-10. Dissolution of the extracellular traps by DNase I partly abrogated the T cell suppression exerted by eosinophils. Extracellular trap formation has mainly been associated with anti-bacterial defense, but we show a new putative function of these cellular formations, as mediators of T cell suppression by enabling the release of galectin-10 from eosinophils.
|
|
| 21. |
|
|
| 22. |
- Lundell, Anna-Carin, 1976, et al.
(author)
-
Dihydrotestosterone levels at birth associate positively with higher proportions of circulating immature/naïve CD5+ B cells in boys.
- 2017
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
-
Journal article (peer-reviewed)abstract
- Boys present with higher proportions of immature/naïve CD5+ B cells than girls up to 3 years of age. Boys also have higher fractions of regulatory T cells (Tregs) in early infancy, but the mechanisms for these sex-related differences are unknown. In the prospective FARMFLORA follow-up study of 23 boys and 25 girls, we investigated if these immunological differences remained at 8 years of age. We also examined if testosterone or dihydrotestosterone (DHT) levels at birth and at 8 years of age were associated with immune maturation. Immunological variables and androgen levels were examined and measured in blood samples obtained at birth, 3-5 days and at 8 years of age. Boys had higher proportions of CD5+ and immature/transitional CD24hiCD38hi B cells, whereas girls had higher fractions of B cells with a memory phenotype at 8 years of age. School-aged boys also presented with higher frequencies of Tregs, and a greater capacity to produce T-cell-associated cytokines. Among boys, higher cord blood DHT levels were associated with higher proportions of CD5+ B cells in early infancy and at 8 years of life. These results suggest that DHT actions in utero might be involved in the mechanism for delayed peripheral B-cell maturation in boys.
|
|
| 23. |
- Lundell, Anna-Carin, 1976, et al.
(author)
-
IFN type I and II induce BAFF secretion from human decidual stromal cells
- 2017
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
-
Journal article (peer-reviewed)abstract
- B cell activating factor (BAFF) is a critical cytokine for maturation of immature B cells. In murine lymph nodes, BAFF is mainly produced by podoplanin-expressing stromal cells. We have previously shown that circulating BAFF levels are maximal at birth, and that farmers' children exhibit higher BAFF levels in cord blood than non-farmers' children. Here, we sought to investigate whether maternal-derived decidual stromal cells from placenta secrete BAFF and examine what factors could stimulate this production. We found that podoplanin is expressed in decidua basalis and in the underlying villous tissue as well as on isolated maternal-derived decidual stromal cells. Decidual stromal cells produced BAFF when stimulated with IFN-gamma and IFN-alpha, and NK cells and NK-T-like cells competent of IFN-gamma production were isolated from the decidua. Finally, B cells at different maturational stages are present in decidua and all expressed BAFF-R, while stromal cells did not. These findings suggest that decidual stromal cells are a cellular source of BAFF for B cells present in decidua during pregnancy.
|
|
| 24. |
- Lundell, Anna-Carin, 1976, et al.
(author)
-
Soluble CD14 and CD83 from human neonatal antigen-presenting cells are inducible by commensal bacteria and suppress allergen-induced human neonatal Th2 differentiation
- 2007
-
In: Infect Immun. ; 75:8, s. 4097-104
-
Journal article (peer-reviewed)abstract
- CD14 is expressed on the cell surface of various antigen-presenting cells, and CD83 is a maturation marker for dendritic cells (DC). CD14 and CD83 are also present as soluble proteins, and both have immunoregulatory functions. We examined whether neonatal cord blood monocytes or DC released soluble CD14 (sCD14) or sCD83 when exposed to the commensal intestinal bacteria Clostridium perfringens, Staphylococcus aureus, Lactobacillus rhamnosus, Escherichia coli, and Bacteroides fragilis. We found that the gram-positive bacteria C. perfringens and S. aureus, but not gram-negative bacteria, induced the release of sCD14 from monocytes. DC, on the other hand, released sCD14 in response to both gram-positive and gram-negative bacteria. Moreover, the expression of the virulence factor staphylococcal protein A seemed to be important for S. aureus-induced sCD14 production from both monocytes and DC. Soluble CD83 was released from DC, but not from monocytes, when exposed to both gram-positive and gram-negative bacteria. Finally, to investigate whether sCD14 or sCD83 could modulate neonatal allergen-induced T-cell differentiation, DC were exposed to birch allergen alone or in the presence of sCD14 or sCD83 and then cocultured with autologous T cells. We demonstrate that sCD14 and sCD83 inhibited the birch allergen-induced Th2 differentiation by suppressing interleukin 13 production. Together, these results suggest that the commensal intestinal flora may be an important stimulus for the developing immune system by inducing the immunoregulatory proteins sCD14 and sCD83, which may be involved in preventing T-cell sensitization to allergens in infants.
|
|
| 25. |
|
|
| 26. |
- Pandya, Jayesh M., et al.
(author)
-
Blood chemokine profile in untreated early rheumatoid arthritis: CXCL10 as a disease activity marker
- 2017
-
In: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 19:1
-
Journal article (peer-reviewed)abstract
- © 2017 The Author(s).Background: We have recently analyzed the profile of T-cell subtypes based on chemokine receptor expression in blood from untreated early rheumatoid arthritis (ueRA) patients compared to healthy controls (HC). Here, we compared the levels of the respective chemokines in blood plasma of ueRA patients with those of HC. We also studied the association of chemokine levels with the proportions of circulating T-cell subsets and the clinical disease activity. Methods: Peripheral blood was obtained from 43 patients with ueRA satisfying the ACR 2010 criteria and who had not received any disease-modifying anti-rheumatic drugs (DMARD) or prednisolone, and from 14 sex- and age-matched HC. Proportions of T helper cells in blood, including Th0, Th1, Th2, Th17, Th1Th17, TFh, and regulatory T cells, were defined by flow cytometry. Fifteen chemokines, including several CXCL and CCL chemokines related to the T-cell subtypes as well as to other major immune cells, were measured in blood plasma using flow cytometry bead-based immunoassay or ELISA. Clinical disease activity in patients was evaluated by assessing the following parameters: Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), swollen joint counts (SJC), tender joint counts (TJC), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The data were analyzed using multivariate factor analyses followed by univariate analyses. Results: Multivariate discriminant analysis showed that patients with ueRA were separated from HC based on the blood plasma chemokine profile. The best discriminators were CXCL9, CXCL10, CXCL13, CCL4, and CCL22, which were significantly higher in ueRA compared to HC in univariate analyses. Among the chemokines analyzed, only CXCL10 correlated with multiple disease activity measures, including DAS28-CRP, DAS28-ESR, CDAI, SJC in 66 joints, CRP, and ESR. Conclusions: High circulating levels of CXCL10 in the plasma of ueRA patients and the association with the clinical disease activity suggests that CXCL10 may serve as a disease activity marker in early rheumatoid arthritis.
|
|
| 27. |
- Pandya, Jayesh M., et al.
(author)
-
Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects
- 2016
-
In: Journal of Leukocyte Biology. - 0741-5400. ; 100:4, s. 823-833
-
Journal article (peer-reviewed)abstract
- The pathogenic role and frequency of T cell subtypes in early rheumatoid arthritis are still unclear. We therefore performed a comprehensive analysis of the circulating T cell subtype pattern in patients with untreated early rheumatoid arthritis compared to healthy control subjects. Peripheral bloodmononuclear cells were obtained from 26 patients with untreated early rheumatoid arthritis and from with 18 age-and sex-matched healthy control subjects. T helper cell types Th0, Th1, Th2, Th17, and Th1/17 and nonclassic T helper subsets were defined by flow cytometry based on the expression of chemokine receptors CCR4, CCR6, and CXCR3. Regulatory T cells were defined by expression of CD25(+) CD127(low) and also FOXP3. CXCR5(+) cells among regulatory and nonregulatory T cells were defined as T follicular regulatory and T follicular helper cells, respectively. The phenotype of T cell subsets was confirmed by transcription factor and cytokine secretion analyses. Multivariate discriminant analysis showed that patients with untreated early rheumatoid arthritis were segregated from healthy control subjects based on the circulating T cell subset profile. Among the discriminator subsets, CCR4(+)CXCR3(-) (Th2 and Th17), CTLA4(+) and FOXP3(+) subsets were present in significantly higher frequencies, whereas CCR42 (Th1/Th17, CCR6(+)CCR4(-) CXCR3(-), and Th1) subsets were present in lower frequencies in patients with untreated early rheumatoid arthritis compared with healthy control subjects. The proportions of Th2 and Th17 subsets associated positively with each other and negatively with the CXCR3(+)/interferon gamma-secreting subsets (Th1 and Th1/Th17) in patients with untreated rheumatoid arthritis. The proportions of Th2 cells increased with age in patients with untreated early rheumatoid arthritis and healthy control subjects. The dominance of circulating CCR4(+) CXCR3(-) T helper subsets (Th2 and Th17) in untreated early rheumatoid arthritis point toward a pathogenic role of these cells in early stages of the disease.
|
|
| 28. |
- Rabe, Hardis, et al.
(author)
-
Higher proportions of circulating FOXP3+ and CTLA-4+ regulatory T cells are associated with lower fractions of memory CD4+ T cells in infants.
- 2011
-
In: Journal of leukocyte biology. - : Oxford University Press (OUP). - 1938-3673 .- 0741-5400. ; 90:6, s. 1133-40
-
Journal article (peer-reviewed)abstract
- In adults, a majority of FOXP3(+) T(regs) expresses CTLA-4, and this costimulatory molecule is essential to control the expansion of other T cells. However, it remains to be investigated whether FOXP3(+) and/or CTLA-4(+) T(regs) are associated with the expression of memory markers and homing receptors on CD4(+) T cells. Thus, in a prospective newborn-infant cohort study, we examined the proportions of FOXP3(+) and CTLA-4(+) T(regs) within the CD4(+)CD25(+) T cell population and the fractions of CD4(+) T cells that expressed CD45RA, CD45RO, HLA-DR, α(4)β(7), CD62L, and CCR4 at several time-points during the first 3 years of life using flow cytometry. With the use of multivariate factor analysis, we found that a high proportion of FOXP3(+) or CTLA-4(+) T(regs) during the first 18 months of life was associated positively with the fraction of T cells that expressed a naïve phenotype (CD45RA and α(4)β(7)) and inversely related to the fraction of T cells that expressed a memory phenotype (CD45RO and CCR4) later in childhood. In conclusion, FOXP3(+) or CTLA-4(+) T(regs) may modulate CD4(+) T cell activation and homing receptor expression in children.
|
|
| 29. |
- Rabe, Hardis, et al.
(author)
-
Neonatal gut colonization by Bifidobacterium is associated with higher childhood cytokine responses.
- 2020
-
In: Gut microbes. - : Informa UK Limited. - 1949-0984 .- 1949-0976. ; 12:1, s. 1-14
-
Journal article (peer-reviewed)abstract
- The gut microbiota is a major stimulus for the immune system, and late acquisition of bacteria and/or reduced complexity of the gut flora may delay adaptive immune maturation. However, it is unknown how the gut bacterial colonization pattern in human infants is related to T cell activation during early childhood. We followed 65 Swedish children in the FARMFLORA cohort, from birth up to 3years of age. In fecal samples collected at several time points during the first year of life, the gut colonization pattern was investigated with the use of both 16S rRNA next generation sequencing (NGS) and culture-based techniques. This was related to production of IL-13, IL-5, IL-6, TNF, IL-1β and IFN-γ by PHA-stimulated fresh mononuclear cells and to proportions of CD4+ T cells that expressed CD45RO at 36months of age. Both NGS and culture-based techniques showed that colonization by Bifidobacterium at 1week of age associated with higher production of IL-5, IL-6, IL-13, TNF and IL-1β at 36months of age. By contrast, gut colonization by Enterococcus, Staphylococcus aureus or Clostridium in early infancy related inversely to induced IL-13, IL-5 and TNF at 3years of age. Infants with elder siblings produced more cytokines and had a larger fraction of CD45RO+ T cells compared to single children. However, controlling for these factors did not abolish the effect of colonization by Bifidobacterium on immune maturation. Thus, gut colonization in early infancy affects T cell maturation and Bifidobacterium may be especially prone to induce infantile immune maturation.
|
|
| 30. |
- Rabe, Hardis, et al.
(author)
-
Staphylococcus aureus convert neonatal conventional CD4(+) T cells into FOXP3(+) CD25(+) CD127(low) T cells via the PD-1/PD-L1 axis
- 2014
-
In: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 141:3, s. 467-481
-
Journal article (peer-reviewed)abstract
- The gut microbiota provides an important stimulus for the induction of regulatory T (Treg) cells in mice, whether this applies to newborn children is unknown. In Swedish children, Staphylococcus aureus has become a common early colonizer of the gut. Here, we sought to study the effects of bacterial stimulation on neonatal CD4(+) T cells for the induction of CD25(+)CD127(low) Treg cells in vitro. The proportion of circulating CD25(+)CD127(low) Treg cells and their expression of FOXP3, Helios and CTLA-4 was examined in newborns and adults. To evaluate if commensal gut bacteria could induce Treg cells, CellTrace violet-stained non-Treg cells from cord or peripheral blood from adults were co-cultured with autologous CD25(+)CD127(low) Treg cells and remaining mononuclear cells and stimulated with S.aureus. Newborns had a significantly lower proportion of CD25(+)CD127(low) Treg cells than adults, but these cells were Helios(+) and CTLA-4(+) to a higher extent than in adults. FOXP3(+)CD25(+)CD127(low) T cells were induced mainly in neonatal CellTrace-stained non-Treg cells after stimulation with S.aureus. In cell cultures from adults, S.aureus induced CD25(+)CD127(low) T cells only if sorted naive CD45RA(+) non-Treg cells were used, but these cells expressed less FOXP3 than those induced from newborns. Sorted neonatal CD25(+)CD127(low) T cells from S.aureus-stimulated cultures were still suppressive. Finally, blocking PD-L1 during stimulation reduced the induction of FOXP3(+)CD25(+)CD127(low) T cells. These results suggest that newborns have a higher proportion of circulating thymically derived Helios(+) Treg cells than adults and that S.aureus possess an ability to convert neonatal conventional CD4(+) T cells into FOXP3(+)CD25(+) CD127(low) Treg cells via the PD-1/PD-L1 axis.
|
|
| 31. |
- Stockfelt, Marit, et al.
(author)
-
Plasma interferon-alpha is associated with double-positivity for autoantibodies but is not a predictor of remission in early rheumatoid arthritis-a spin-off study of the NORD-STAR randomized clinical trial
- 2021
-
In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 23:1
-
Journal article (peer-reviewed)abstract
- Background The type I interferon (IFN) gene signature is present in a subgroup of patients with early rheumatoid arthritis (RA). Protein levels of IFN alpha have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect. Methods Patients with early untreated RA (n = 347) were randomized to methotrexate combined with prednisone, certolizumab-pegol, abatacept, or tocilizumab. Plasma IFN alpha protein levels were determined by single molecular array (Simoa) before and 24 weeks after treatment initiation and were related to demographic and clinical factors including clinical disease activity index, disease activity score in 28 joints, swollen and tender joint counts, and patient global assessment. Results IFN alpha protein positivity was found in 26% of the patients, and of these, 92% were double-positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). IFN alpha protein levels were reduced 24 weeks after treatment initiation, and the absolute change was similar irrespective of treatment. IFN alpha protein positivity was associated neither with disease activity nor with achievement of CDAI remission 24 weeks after randomization. Conclusion IFN alpha protein positivity is present in a subgroup of patients with early RA and associates with double-positivity for autoantibodies but not with disease activity. Pre-treatment IFN alpha positivity did not predict remission in any of the treatment arms, suggesting that the IFN alpha system is distinct from the pathways of TNF, IL-6, and T-cell activation in early RA. A spin-off study of the NORD-STAR randomized clinical trial, NCT01491815 (ClinicalTrials), registered 12/08/2011, .
|
|
| 32. |
- Strömbeck, Anna, et al.
(author)
-
Delayed adaptive immunity is related to higher MMR vaccine-induced antibody titers in children
- 2016
-
In: Clinical & Translational Immunology. - : Wiley. - 2050-0068. ; 5
-
Journal article (peer-reviewed)abstract
- There are notable inter-individual variations in vaccine-specific antibody responses in vaccinated children. The aim of our study was to investigate whether early-life environmental factors and adaptive immune maturation prior and close to measles-mumps-rubella (MMR) immunization relate to magnitudes of vaccine-specific antibody titers. In the FARMFLORA birth cohort, including both farming and non-farming families, children were immunized with the MMR vaccine at 18 months of age. MMR vaccine-induced antibody titers were measured in plasma samples obtained at 36 months of age. Infants' blood samples obtained at birth, 3-5 days and at 4 and 18 months of age were analyzed for T- and B-cell numbers, proportions of naive and memory T and B cells, and fractions of putative regulatory T cells. Multivariate factor analyses show that higher anti-MMR antibody titers were associated with a lower degree of adaptive immune maturation, that is, lower proportions of memory T cells and a lower capacity of mononuclear cells to produce cytokines, but with higher proportions of putative regulatory T cells. Further, children born by cesarean section (CS) had significantly higher anti-measles titers than vaginally-born children; and CS was found to be associated with delayed adaptive immunity. Also, girls presented with significantly higher anti-mumps and anti-rubella antibody levels than boys at 36 months of age. These results indicate that delayed adaptive immune maturation before and in close proximity to immunization seems to be advantageous for the ability of children to respond with higher anti-MMR antibody levels after vaccination.
|
|
| 33. |
- Strömbeck, Anna, et al.
(author)
-
Earlier infantile immune maturation is related to higher DTP vaccine responses in children
- 2016
-
In: Clinical & Translational Immunology. - : Wiley. - 2050-0068. ; 5
-
Journal article (peer-reviewed)abstract
- There are large inter-individual variations in vaccine-specific antibody responses in children. We sought to investigate whether early-life environmental factors and/or adaptive immune maturation were related to diphtheria-tetanus-pertussis (DTP) vaccine-specific antibody levels at 18 months of age. In the prospective FARMFLORA birth-cohort, including both farming and non-farming families, children were immunized with DTP vaccine at 3, 5 and 12 months of age. DTP vaccine-induced antibody levels were measured in plasma at 18 months of age. Infants' blood samples obtained at birth, 3-5 days, 4, 18 and 36 months and at 8 years of age were analyzed for total CD4(+) T- and B-cell counts, proportions of naive and memory T and B cells, and fractions of putative regulatory T cells by flow cytometry. Multivariate factor analysis was used to examine associations between immune variables and vaccine responses. The most apparent multivariate pattern was that higher anti-DTP antibody titers at 18 months of age were associated with lower infantile total counts of T and B cells in the blood. Furthermore, lower infantile total T-and B-cell blood counts were associated with higher proportions of circulating CD45RO(+) memory T cells and to lower proportions of alpha 4 beta 7(+) naive T cells later in childhood. The multivariate findings were corroborated in univariate correlation analyses. Sex, delivery mode and dairy farm exposure were unrelated to the magnitude of DTP-specific antibody responses. Our results thus suggest that children with a more mature/activated infantile adaptive immunity respond with higher vaccine-induced anti-DTP antibody levels at 18 months of age.
|
|
| 34. |
|
|
| 35. |
|
|
