| 1. |
- Ambrosi, Aurelie, et al.
(author)
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Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern
- 2012
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In: Annals of the Rheumatic Diseases. - London : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 71:3, s. 334-340
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Journal article (peer-reviewed)abstract
- Objective Congenital heart block may develop in the fetuses of Ro/SSA-positive and La/SSB-positive mothers. Recurrence rates of only 10-20% despite persisting maternal antibodies indicate that additional factors are critical for the establishment of heart block. The authors investigated the influence of other maternal and fetal factors on heart block development in a Swedish population-based cohort. less thanbrgreater than less thanbrgreater thanMethods The influence of fetal gender, maternal age, parity and time of birth on heart block development was analysed in 145 families, including Ro/La-positive (n=190) and Ro/La-negative (n=165) pregnancies. less thanbrgreater than less thanbrgreater thanResults There was a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was, however, significantly higher than in pregnancies resulting in babies without heart block (pandlt;0.05). Seasonal timing of pregnancy influenced the outcome. Gestational susceptibility weeks 18-24 occurring during January-March correlated with a higher proportion of children with heart block and lower vitamin D levels during the same period in a representative sample of Swedish women and a corresponding higher proportion of children with heart block born in the summer (pandlt;0.02). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies. less thanbrgreater than less thanbrgreater thanConclusion This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for heart block development in children of Ro/La-positive women. These observations may be useful for counselling when pregnancy is considered.
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| 2. |
- Asker, Martin, et al.
(author)
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Preseason clinical shoulder test results and shoulder injury rate in adolescent elite handball players : a prospective study
- 2020
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In: Journal of Orthopaedic and Sports Physical Therapy. - : Journal of Orthopaedic & Sports Physical Therapy (JOSPT). - 0190-6011 .- 1938-1344. ; 50:2, s. 67-74
-
Journal article (peer-reviewed)abstract
- STUDY DESIGN: Prospective cohort study.BACKGROUND: Shoulder injuries are common in handball. Shoulder weakness, scapular dyskinesia and range of motion (ROM) deficits are associated with shoulder injury in adults, but studies of adolescent players are scarce.OBJECTIVE: To investigate if elite adolescent female and male handball players with shoulder muscle weakness, deficits in shoulder rotation ROM or joint position sense (JPS), or scapular dyskinesia in preseason have an increased shoulder injury rate compared to players not having these characteristics.METHODS: 341 uninjured players (452 player-seasons, 50% females) had isometric external rotational (IER), internal rotational (IIR), abduction (IABD) and eccentric external rotational (EER) shoulder strength, shoulder ROM, JPS, and scapular dyskinesia measured during pre-season. Players were monitored weekly regarding match- and training hours and shoulder injuries during one or two seasons. We used multivariable Cox proportional hazard models to calculate hazard rate ratios (HRR) related to the first injury with 95% confidence intervals (95% CI).RESULTS: 48 new shoulder injuries were reported during the two seasons. In females, the HRR for IER was 2.37 (95% CI 1.03-5.44), for IIR 2.44 (95% CI 1.06-5.61), and for scapular dyskinesia 1.53 (95% CI 0.36-6.52). In males, the HRR for IER was 1.02 (95% CI 0.44-2.36), for IIR 0.74 (95% CI 0.31-1.75), and for scapular dyskinesia 3.43 (95% CI 1.49-7.92). There were no associations between new shoulder injuries and deficits in ROM or JPS.CONCLUSION: In adolescent elite handball, male players with pre-season scapula dyskinesia, and female players with pre-season internal or external rotation shoulder weakness, had an increased shoulder injury rate. J Orthop Sports Phys Ther, Epub 27 Nov 2019. doi:10.2519/jospt.2020.9044.
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| 3. |
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| 4. |
- Asker, Martin, et al.
(author)
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The effect of shoulder and knee exercise programmes on the risk of shoulder and knee injuries in adolescent elite handball players : A three-armed cluster randomised controlled trial
- 2022
-
In: Sports Medicine - Open. - : Springer Science and Business Media LLC. - 2199-1170 .- 2198-9761. ; 8:1
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The risk of injury in adolescent handball is high, and shoulder and knee injuries are among the most frequent and burdensome. The Swedish Knee Control programme reduced the risk of anterior cruciate ligament injuries in female youth football players and traumatic knee injuries in male and female youth floorball players. However, to date, Knee Control has not been evaluated in an elite youth sport setting. The literature on the prevention of shoulder injuries in sport is scarce, and there are to our knowledge no previous studies evaluating the preventative efficacy of injury prevention exercise programmes (IPEPs) on shoulder injuries in adolescent handball players.OBJECTIVES: To study the preventive efficacy of IPEPs on shoulder and knee injuries in adolescent elite handball players.METHODS: Eighteen Swedish handball-profiled secondary schools (clusters) with players aged 15-19 years, 54% males were randomised into either the Shoulder Group or Knee Group (interventions) or a Control Group. Players in the Shoulder Group were instructed to perform the Shoulder Control programme, and players in the Knee Group to perform the Knee Control programme, three times per week during May 2018 to May 2019. Control Group players continued their usual training. Outcomes were shoulder and knee injuries defined by the Oslo Sports Trauma Research Center Overuse Injury Questionnaire. Intention-to-treat analyses were performed using Cox regression models with hazard rate ratios (HRRs) with corresponding 95% confidence intervals (CI).RESULTS: Six clusters (199 players) in the Shoulder Group, six clusters (216 players) in the Knee Group and six clusters (212 players) in the Control Group were included. There were 100 shoulder injuries and 156 knee injuries. The Shoulder Group had a 56% lower shoulder injury rate, HRR 0.44 (95% CI 0.29 to 0.68), and the Knee Group had a 31% lower knee injury rate, HRR 0.69 (95% CI 0.49 to 0.97) than the Control Group. The absolute risk reduction was 11% and 8%, and the number needed to treat was 9 and 13, respectively.CONCLUSIONS: Adolescent elite handball players who performed the Shoulder Control and the Knee Control programmes had a lower risk of shoulder and knee injuries, respectively, than players who continued their usual training. Further research on how these two programmes can be combined to reduce knee and shoulder injuries in a time effective way is warranted. Trial registration ISRCTN15946352. Key points The burden of knee and shoulder injuries in handball is high. The Shoulder Control programme reduces the risk and overall burden of shoulder injuries in adolescent elite handball players. The Knee Control programme reduces the risk and overall burden of knee injuries in adolescent elite handball players.
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| 5. |
- Björkman, Per, et al.
(author)
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Common Interactions between S100A4 and S100A9 Defined by a Novel Chemical Probe.
- 2013
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:5
-
Journal article (peer-reviewed)abstract
- S100A4 and S100A9 proteins have been described as playing roles in the control of tumor growth and metastasis. We show here that a chemical probe, oxyclozanide (OX), selected for inhibiting the interaction between S100A9 and the receptor for advanced glycation end-products (RAGE) interacts with both S100A9 and S100A4. Furthermore, we show that S100A9 and S100A4 interact with RAGE and TLR4; interactions that can be inhibited by OX. Hence, S100A4 and S100A9 display similar functional elements despite their primary sequence diversity. This was further confirmed by showing that S100A4 and S100A9 dimerize both in vitro and in vivo. All of these interactions required levels of Zn(++) that are found in the extracellular space but not intracellularly. Interestingly, S100A4 and S100A9 are expressed by distinct CD11b(+) subpopulations both in healthy animals and in animals with either inflammatory disease or tumor burden. The functions of S100A9 and S100A4 described in this paper, including heterodimerization, may therefore reflect S100A9 and S100A4 that are released into the extra-cellular milieu.
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| 6. |
- Briem, Oscar, et al.
(author)
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CD169+ Macrophages in Primary Breast Tumors Associate with Tertiary Lymphoid Structures, Tregs and a Worse Prognosis for Patients with Advanced Breast Cancer
- 2023
-
In: Cancers. - : MDPI AG. - 2072-6694. ; 15:4
-
Journal article (peer-reviewed)abstract
- The presence of CD169+ macrophages in the draining lymph nodes of cancer patients is, for unknown reasons, associated with a beneficial prognosis. We here investigated the prognostic impact of tumor-infiltrating CD169+ macrophages in primary tumors (PTs) and their spatial relation to tumor-infiltrating B and T cells. Using two breast cancer patient cohorts, we show that CD169+ macrophages were spatially associated with the presence of B and T cell tertiary lymphoid-like structures (TLLSs) in both PTs and lymph node metastases (LNMs). While co-infiltration of CD169+/TLLS in PTs correlated with a worse prognosis, the opposite was found when present in LNMs. RNA sequencing of breast tumors further confirmed that SIGLEC1 (CD169) expression was associated with mature tertiary lymphoid structure (TLS), and Treg and Breg signatures. We propose that the negative prognostic value related to CD169+ macrophages in PTs is a consequence of an immunosuppressive tumor environment rich in TLSs, Tregs and Bregs.
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| 7. |
- Chakraborty, Paramita, et al.
(author)
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Vesicular Location and Transport of S100A8 and S100A9 Proteins in Monocytoid Cells.
- 2015
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:12
-
Journal article (peer-reviewed)abstract
- We show here, by using surface biotinylation, followed by Western blotting or surface plasmon resonance analysis, that very low levels of S100A8 and/or S100A9 can be detected on the surface of THP-1 cells or freshly isolated human monocytes. This was supported by immune-electron microscopy where we observed membrane-associated expression of the proteins restricted to small patches. By using confocal microscopy we could determine that S100A8 and S100A9 protein in THP-1 cells or freshly isolated human monocytes was mostly present in vesicular structures. This finding was confirmed using immune-electron microscopy. Subcellular fractionation and confocal microscopy showed that these vesicular structures are mainly early endosomes and endolysosomes. Our subsequent studies showed that accumulation of S100A8 and S100A9 in the endolysosomal compartment is associated with induction of their release from the cells. Furthermore, an inhibitor of lysosomal activity could modulate the release of S100A8 and S100A9 in the extracellular milieu. Our current results suggest that the S100A8 and S100A9 proteins are primarily associated with certain kinds of cytosolic vesicles and may be secreted via an endolysosomal pathway.
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| 8. |
- Erlandsson, Lena, et al.
(author)
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Joining chain-expressing and -nonexpressing B cell populations in the mouse
- 2001
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In: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 194:5, s. 557-570
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Journal article (peer-reviewed)abstract
- The diphtheria toxin A chain (DTA) was gene targeted into the Joining chain (J chain) locus to create a mouse strain selecting against J chain-expressing cells, JDTA mice. Serum immunoglobulin (Ig)M and serum IgG were reduced six to eightfold, while serum IgA was elevated 14-fold in these mice. JDTA mice were immune competent although the serum Ig response compared with wild-type mice was reduced sixfold at day 14 but only fourfold at day 45 after immunization. Exchanging the DTA gene with a cDNA for c-myc resulted in mice with a distinct phenotype with increased Ig production and enhanced humoral immune responses. Analysis of single B cells stimulated by lipopolysaccharide in vitro using reverse transcription-polymerase chain reaction showed that J chain-nonexpressing B cells could be detected that had a secretory phenotype as determined by an abundance of transcript for secretory IgM. Finally, limiting dilution analysis of peripheral B cells showed that J chain expression was a clonal property already established in naive, peripheral B lymphocytes.
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| 9. |
- Fältström, Anne, et al.
(author)
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Lifestyle characteristics in adolescent female football players : data from the Karolinska football Injury Cohort.
- 2022
-
In: BMC Sports Science, Medicine and Rehabilitation. - : BioMed Central (BMC). - 2052-1847. ; 14:1
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Normative values of lifestyle characteristics in adolescent female football players may be used by clinicians and coaches to take actions because the potential important for well-being, performance on the pitch, and risk of injury. The aim was to report descriptive characteristics of lifestyle factors in adolescent female football players and potential changes over 1 year.METHODS: We included 419 adolescent competitive female football players from 12 clubs and 27 teams (age 14 ± 1 years, range 12-17 years) and 286 were followed over 1 year. The players completed an extensive questionnaire regarding demographics, football-related factors, and lifestyle factors including tobacco consumption, alcohol use, medicine intake, eating and sleeping habits, well-being, stress, coping, and passion. Baseline data are presented for the total cohort and separately for 4 age groups (12, 13, 14, and 15-17 years).RESULTS: 12% skipped breakfast, 8% skipped lunch and 11% used protein supplements several days per week. 16% slept less than 8 h/night, 8% had impaired sleep with daytime consequences, and 22% stated that they were tired in daily activities several days per week. 32% experienced stress some or most days/week and 24% were classified as having psychological distress. Medicine intake (23% vs. 34%), skipping breakfast or lunch several days per week (10% vs. 47% and 20 vs. 33%), tiredness (20% vs. 27%), stress (26% vs. 40%), and psychological distress (27% vs. 37%) increased significantly (P = 0.031 to < 0.001) at the 1-year follow-up.CONCLUSION: Many adolescent female football players skip breakfast and lunch, have insufficient sleep, experience stress and are classified as having psychological distress. These factors increased over 1 year.
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| 10. |
- Fältström, Anne, et al.
(author)
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Normative values and changes in range of motion, strength, and functional performance over 1 year in adolescent female football players : Data from 418 players in the Karolinska football Injury Cohort study.
- 2022
-
In: Physical Therapy in Sport. - : Elsevier. - 1466-853X .- 1873-1600. ; 58, s. 106-116
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To study normative values of range of motion (ROM), strength, and functional performance and investigate changes over 1 year in adolescent female football players.DESIGN: Cross-sectional.PARTICIPANTS: 418 adolescent female football players aged 12-17 years.MAIN OUTCOME MEASURES: The physical characteristic assessments included (1) ROM assessment of the trunk, hips, and ankles; (2) strength measures (maximal isometric and eccentric strength for the trunk, hips, and knees, and strength endurance for the neck, back, trunk and calves), and (3) functional performance (the one-leg long box jump test and the square hop test).RESULTS: Older players were stronger, but not when normalized to body weight. Only small differences in ROM regarding age were found. ROM increased over 1 year in most measurements with the largest change in hip external rotation, which increased by 6-7° (Cohen's d = 0.83-0.87). Hip (d = 0.28-1.07) and knee (d = 0.38-0.53) muscle strength and the square hop test (d = 0.71-0.99) improved over 1 year.CONCLUSIONS: Normative values for ROM and strength assessments of neck, back, trunk, hips, knees, calves and ankles are presented for adolescent female football players. Generally, fluctuations in ROM were small with little clinical meaning, whereas strength improved over 1 year.
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| 11. |
- Gunnarsdottir, Frida Björk, et al.
(author)
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Breast cancer associated CD169(+) macrophages possess broad immunosuppressive functions but enhance antibody secretion by activated B cells
- 2023
-
In: Frontiers in Immunology. - 1664-3224. ; 14
-
Journal article (peer-reviewed)abstract
- CD169(+) resident macrophages in lymph nodes of breast cancer patients are for unknown reasons associated with a beneficial prognosis. This contrasts CD169(+) macrophages present in primary breast tumors (CD169(+) TAMs), that correlate with a worse prognosis. We recently showed that these CD169(+) TAMs were associated with tertiary lymphoid structures (TLSs) and T-regs in breast cancer. Here, we show that CD169(+) TAMs can be monocyte-derived and express a unique mediator profile characterized by type I IFNs, CXCL10, PGE(2) and inhibitory co-receptor expression pattern. The CD169(+) monocyte-derived macrophages (CD169(+) Mo-M) possessed an immunosuppressive function in vitro inhibiting NK, T and B cell proliferation, but enhanced antibody and IL6 secretion in activated B cells. Our findings indicate that CD169(+) Mo-M in the primary breast tumor microenvironment are linked to both immunosuppression and TLS functions, with implications for future targeted Mo-M therapy.
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| 12. |
- Gunnarsdóttir, Frida Björk, et al.
(author)
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Inflammatory macrophage derived TNFα downregulates estrogen receptor α via FOXO3a inactivation in human breast cancer cells
- 2020
-
In: Experimental Cell Research. - : Elsevier BV. - 0014-4827. ; 390:1
-
Journal article (peer-reviewed)abstract
- Patients with estrogen receptor α positive (ERα+) breast cancer can respond to endocrine therapy, but treatment resistance is common and associated with downregulation of ERα expression in the dormant residual cells. Here we show, using long-term NSG xenograft models of human breast cancer and primary human monocytes, in vitro primary cell cultures and tumors from breast cancer patients, that macrophage derived tumor necrosis factor alpha (TNFα) downregulates ERα in breast cancer cells via inactivation of the transcription factor Forkhead box O transcription factor 3a (FOXO3a). Moreover, presence of tumor associated macrophages in the primary tumor of breast cancer patients, was associated with ERα negativity, and with worse prognosis in patients with ERα+ tumors. We propose that pro-inflammatory macrophages, despite being tumoricidal, may have direct effects on tumor progression and endocrine resistance in breast cancer patients. Our findings suggest that TNFα antagonists should be evaluated for treatment of ERα+ breast cancer.
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| 13. |
- Johansson, Fred, et al.
(author)
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Strengths of associations between depressive symptoms and loneliness, perfectionistic concerns, risky alcohol use and physical activity across levels of sleep quality in Swedish university students : A cross-sectional study
- 2023
-
In: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 32:2
-
Journal article (peer-reviewed)abstract
- Previous research shows that sleep quality may interact with some other predictors of depression, such that poor sleep could strengthen the association between these factors and depression. We aimed to determine the presence of statistical interactions between sleep quality and loneliness, risky alcohol use, perfectionistic concerns and/or physical inactivity in relation to depressive symptoms. Further, we aimed to describe the functional form of the statistical interactions and associations. We used a cross-sectional design and included 4262 Swedish university students. All measures were self-reported, sleep quality was measured with the Pittsburgh Sleep Quality Index, and depressive symptoms with the short-form Depression, Anxiety and Stress Scale. Regression models of increasing complexity (linear and non-linear, with and without interactions) were compared to determine the presence of associations and statistical interactions, and to explore the best functional form for these associations and interactions. Out-of-sample R2 from repeated cross-validation was used to select the final models. We found that sleep quality was associated with depressive symptoms in all final models. Sleep quality showed a linear interaction with perfectionistic concerns in relation to depressive symptoms, such that perfectionistic concerns were more strongly associated with depressive symptoms when sleep quality was poor. Loneliness, risky alcohol use and physical inactivity were non-linearly associated with depressive symptoms but did not interact with sleep quality. We concluded that out of the four examined variables, only perfectionistic concerns interacted with sleep quality in relation to depressive symptoms. This interaction was weak and explained little of the overall variance in depressive symptoms.
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| 14. |
- Kelkka, Tiina, et al.
(author)
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Mice Lacking NCF1 Exhibit Reduced Growth of Implanted Melanoma and Carcinoma Tumors
- 2013
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12, s. e84148-
-
Journal article (peer-reviewed)abstract
- The NADPH oxidase 2 (NOX2) complex is a professional producer of reactive oxygen species (ROS) and is mainly expressed in phagocytes. While the activity of the NOX2 complex is essential for immunity against pathogens and protection against autoimmunity, its role in the development of malignant tumors remains unclear. We compared wild type and Ncf1(m1J) mutated mice, which lack functional NOX2 complex, in four different tumor models. Ncf1(m1J) mutated mice developed significantly smaller tumors in two melanoma models in which B16 melanoma cells expressing a hematopoietic growth factor FLT3L or luciferase reporter were used. Ncf1(m1J) mutated mice developed significantly fewer Lewis Lung Carcinoma (LLC) tumors, but the tumors that did develop, grew at a pace that was similar to the wild type mice. In the spontaneously arising prostate carcinoma model (TRAMP), tumor growth was not affected. The lack of ROS-mediated protection against tumor growth was associated with increased production of immunity-associated cytokines. A significant increase in Th2 associated cytokines was observed in the LLC model. Our present data show that ROS regulate rejection of the antigenic B16-luc and LLC tumors, whereas the data do not support a role for ROS in growth of intrinsically generated tumors.
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| 15. |
- Källberg, Eva, et al.
(author)
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A subset of dendritic cells express joining chain (J-chain) protein
- 2008
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In: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 129:4, s. 590-599
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Journal article (peer-reviewed)abstract
- Joining chain (J-chain) is well known as an integrated component of dimeric immunoglobulin A (IgA) and pentameric IgM. We show here that the J-chain protein is also expressed in a subset of CD11c+ dendritic cells (DC) in C57BL/6 mice. J-chain knockout mice (J−/− mice) had a reduced fraction of CD4−/CD8α+ and mPDCA-1+ DC in the spleen. J−/− mice also had reduced levels of RNA for the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) in the spleen. Furthermore, in lymph nodes from C57BL/6 mice the majority of J-chain-expressing CD11c+ cells also expressed IDO, while the number of IDO-expressing cells in lymph nodes and the amount of IDO protein in splenic CD11c+ cells were reduced in J−/− mice. Also, J−/− mice had a lower ratio of kynurenine/tryptophan in serum compared to C57BL/6 mice, indicating a lower overall IDO activity in J−/− mice. We also show that J−/− mice are less susceptible to tolerance induction than C57BL/6 mice. In conclusion, our data show that J-chain protein is expressed outside the B-cell compartment in a subset of immunoregulatory DC that are compromised in animals that cannot express J-chain.
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| 16. |
- Källberg, Eva, et al.
(author)
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AIRE is expressed in breast cancer TANs and TAMs to regulate the extrinsic apoptotic pathway and inflammation
- 2024
-
In: Journal of Leukocyte Biology. - 1938-3673. ; 115:4, s. 664-678
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Journal article (peer-reviewed)abstract
- Autoimmune regulator (AIRE) is a transcriptional regulator expressed in the thymus and necessary for maintaining immunological self-tolerance. Extra-thymic AIRE expression is rare and a role for AIRE in tumor-associated innate immune cells has not yet been established. In this study we show that AIRE is expressed in human pro-tumor neutrophils. In breast cancer, AIRE was primarily located to tumor associated neutrophils (TANs), and to a lesser extent to tumor associated macrophages (TAMs) and tumor cells. Expression of AIRE in TAN/TAMs, but not in cancer cells, was associated with an adverse prognosis. We show that the functional role for AIRE in neutrophils and macrophages is to regulate expression of immune mediators and the extrinsic apoptotic pathway involving the Fas/TNFR death receptors and Cathepsin G. We here propose that the role for AIRE in TAN/TAMs in breast tumors is to regulate cell death and inflammation, thus promoting tumor progression.
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| 17. |
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| 18. |
- Källberg, Eva, et al.
(author)
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Analysis of somatic mutation activity in multiple V kappa genes involved in the response to 2-phenyl-5-oxazolone
- 1993
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In: International Immunology. - : Oxford University Press (OUP). - 0953-8178 .- 1460-2377. ; 5:6, s. 81-573
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Journal article (peer-reviewed)abstract
- We have studied somatic mutation activity early in a response to 2-phenyl-5-oxazolone coupled to ovalbumin (phOx-OVA). Although the V kappa Ox1 gene rearranged to J kappa 5 is known to predominate in this response, other closely related V kappa genes are involved. We compared the introduction of point mutations into V kappa Ox1 genes and into a set of related V kappa genes rearranged to the same J kappa segment at two time points after primary immunization. The result showed that quantitation of mutations in a single rearrangement substrate leads to an underestimation of the total mutational activity. There is pronounced somatic mutation activity early within genes that may be absent later in the response. We also show that multiple somatic mutations can be detected in B cells from draining lymph nodes after foot-pad injection with phOx-OVA already at day 7 after immunization. The data suggest a system in which mutation acts early in the response on a wide range of substrates and that selection and expansion of high affinity paratopes occurs later.
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| 19. |
- Källberg, Eva, et al.
(author)
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CD11b(+)Ly6C(++)Ly6G(-) cells show distinct function in mice with chronic inflammation or tumor burden
- 2012
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In: BMC Immunology. - : Springer Science and Business Media LLC. - 1471-2172. ; 13
-
Journal article (peer-reviewed)abstract
- Background: S100A9 has been shown to be important for the function of so called Myeloid Derived Suppressor Cells (MDSC). Cells with a similar phenotype are also involved in pro-inflammatory processes, and we therefore wanted to investigate the gene expression and function of these cells in animals that were either subjected to chronic inflammation, or inoculated with tumors. Methods: CD11b(+)Ly6C(++) and Ly6G(+) cells were isolated from spleen, tumor tissue or inflammatory granulomas. S100A9, Arginase 1 and iNOS gene expression in the various CD11b(+) cell populations was analyzed using Q-PCR. The suppressive activity of the CD11b(+) cell populations from different donors was studied in co-culture experiments. Results: S100A9 was shown to be expressed mainly in splenic CD11b(+)Ly6C(+)G(+) cells both at the RNA and protein level. Arginase I and iNOS expression could be detected in both CD11b(+)Ly6C(+)Ly6G(+) and CD11b(+)Ly6C(+)G(-)/C(++)G(-) derived from tumors or a site of chronic inflammation, but was very low in the same cell populations isolated from the spleen. CD11b(+) cells isolated from mice with peritoneal chronic inflammation were able to stimulate T lymphocytes, while CD11b(+) cells from mice with peritoneal tumors suppressed T cell growth. Conclusion: An identical CD11b(+)Ly6C(++)G(-) cell population appears to have the ability to adopt immune stimulatory or immune suppressive functions dependent on the presence of a local inflammatory or tumor microenvironment. Thus, there is a functional plasticity in the CD11b(+)Ly6C(++)G(-) cell population that cannot be distinguished with the current molecular markers.
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| 20. |
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| 21. |
- Källberg, Eva, et al.
(author)
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Indoleamine 2,3-dioxygenase (IDO) activity influence tumor growth in the TRAMP prostate cancer model
- 2010
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In: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 70:13, s. 1461-1470
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Journal article (peer-reviewed)abstract
- Our results argue for a role for IDO mediated immune suppression in the early stages of prostate cancer progression. However, since the intra-tumor IDO expression in J(-/-) mice was indistinguishable from that of C57BL/6 animals the IDO expression in the tumor tissue appears to be irrelevant for TRAMP tumor incidence.
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| 22. |
- Källberg, Eva, et al.
(author)
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Induction of S100A9 homodimer formation in vivo
- 2018
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In: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X. ; , s. 564-568
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Journal article (peer-reviewed)abstract
- We show here that increased S100A8 and S100A9 protein expression is induced in spleen of animals with active inflammation or with inoculated tumors. In tumor bearing animals an increased expression was also detected in the lung. To further analyze the induced proteins, we performed chemical cross-linking followed by Western blotting. We observed in protein extracts from spleen that both S100A8/S100A9 heterodimers as well as S100A9 homodimers were formed, both after tumor and inflammatory challenge. The cellular source for S100A9 homodimers were CD11b+GR1+ cells. S100A9 homodimers were also secreted into the extracellular space. Lastly, in the spleen from normal and tumor bearing animals cells expressing relatively higher levels of S100A9 compared to S100A8 could be observed by immunohistochemistry. Taken together, these data show that the biologically potent dimeric form of S100A9 is induced in vivo in situations of tumor burden or inflammatory challenge.
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| 23. |
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| 24. |
- Källberg, Eva, et al.
(author)
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Quinoline-3-carboxamides modulate primary T cell-dependent B cell responses but do not inhibit functional immunity.
- 2014
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In: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 79:4, s. 237-243
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Journal article (peer-reviewed)abstract
- The effect of a quinoline-3-carboxamide on the T-cell-dependent B-cell response was investigated in C57BL/6 mice after NP-CGG immunization. The primary serum response to the hapten was slightly inhibited by treatment with a quinoline-3-carboxamide. This inhibition was paralleled by reduced numbers of germinal center B cells and follicular T cells in the spleen up to 21 days after immunization. Also, both the number of germinal centers formed and their size was reduced by quinoline-3-carboxamide treatment. In contrast to the observation in the primary immune response there was no inhibitory effect on the secondary immune response. These data could help to explain how quinoline-3-carboxamides can modulate immune function in autoimmune diseases without being immunosuppressive. This article is protected by copyright. All rights reserved.
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| 25. |
- Källberg, Eva, et al.
(author)
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S100A9 Interaction with TLR4 Promotes Tumor Growth
- 2012
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In: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 7:3, s. e34207-
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Journal article (peer-reviewed)abstract
- By breeding TRAMP mice with S100A9 knock-out (S100A9(-/-)) animals and scoring the appearance of palpable tumors we observed a delayed tumor growth in animals devoid of S100A9 expression. CD11b(+) S100A9 expressing cells were not observed in normal prostate tissue from control C57BL/6 mice but were readily detected in TRAMP prostate tumors. Also, S100A9 expression was observed in association with CD68(+) macrophages in biopsies from human prostate tumors. Delayed growth of TRAMP tumors was also observed in mice lacking the S100A9 ligand TLR4. In the EL-4 lymphoma model tumor growth inhibition was observed in S100A9(-/-) and TLR4(-/-), but not in RAGE(-/-) animals lacking an alternative S100A9 receptor. When expression of immune-regulating genes was analyzed using RT-PCR the only common change observed in mice lacking S100A9 and TLR4 was a down-regulation of TGF beta expression in splenic CD11b(+) cells. Lastly, treatment of mice with a small molecule (ABR-215050) that inhibits S100A9 binding to TLR4 inhibited EL4 tumor growth. Thus, S100A9 and TLR4 appear to be involved in promoting tumor growth in two different tumor models and pharmacological inhibition of S100A9-TLR4 interactions is a novel and promising target for anti-tumor therapies.
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