| 1. |
- Lingblom, Christine, 1984, et al.
(author)
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Topical Corticosteroids Do Not Revert the Activated Phenotype of Eosinophils in Eosinophilic Esophagitis but Decrease Surface Levels of CD18 Resulting in Diminished Adherence to ICAM-1, ICAM-2, and Endothelial Cells.
- 2014
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In: Inflammation. - : Springer Science and Business Media LLC. - 1573-2576 .- 0360-3997. ; 37:6, s. 1932-1944
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Journal article (peer-reviewed)abstract
- Swallowed topical corticosteroids are the standard therapy for eosinophilic esophagitis (EoE) in adults. Eosinophils in the blood of untreated EoE patients have an activated phenotype. Our aim was to determine if corticosteroids restore the phenotype of eosinophils to a healthy phenotype and if certain cell-surface molecules on blood eosinophils correlate with eosinophilic infiltration of the esophagus. Levels of eight surface markers on eosinophils from treated and untreated EoE patients were determined by flow cytometry and analyzed using multivariate methods of pattern recognition. Corticosteroid-treated EoE patients' eosinophils had decreased levels of CD18 compared to both untreated patients and healthy controls, but maintained their activated phenotype. CD18 expression correlated positively with eosinophil numbers in the esophagus and promoted the adherence of eosinophils to ICAM-1, ICAM-2, and to endothelial cells. The diminished expression of CD18 may be one mechanism behind the reduced entry of eosinophils into the esophagus in corticosteroid-treated EoE patients.
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| 2. |
- Ahlmanner, Filip, et al.
(author)
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CD39+ regulatory T cells accumulate in colon adenocarcinomas and display markers of increased suppressive function
- 2018
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9:97, s. 36993-37007
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Journal article (peer-reviewed)abstract
- Increasing knowledge of the function and regulation of tumor-infiltrating lymphocytes has led to new insights in cancer immunotherapy. Regulatory T cells (Treg) accumulate in colon tumors, and we recently showed that CD39+ Treg from cancer patients inhibit transendothelial migration of conventional T cells. CD39 mediates the hydrolysis of ATP to immunosuppressive adenosine and adds to the immunosuppressive effects of Treg. Here, we further investigated the regulatory features of intratumoral CD39+ Treg in colon cancer. Using flow cytometry analyses of cells from 46 colon cancer patients, we confirm the accumulation of CD39+ Treg in the tumor tissue compared to unaffected colon tissue, and also show that tumor-infiltrating Treg express more CD39 and Foxp3 on a per cell basis. Furthermore, CD39+ Treg in tumors express markers indicating increased turnover and suppressive ability. In particular, tumor-infiltrating CD39+ Treg have high expression of surface molecules related to immunosuppression, such as ICOS, PD-L1 and CTLA-4. Functional suppression assays also indicate potent suppressive capacity of CD39+ Treg on proliferation and IFN-γ secretion by conventional T cells. In conclusion, our results identify tumor-infiltrating CD39+ Treg as a numerous and potentially important immunosuppressive subset, and suggest that immunotherapy aimed at reducing the activity of CD39+ Treg may be particularly useful in the setting of colon cancer. © 2018 Ahlmanner et al.
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| 3. |
- Akeus, Paulina, et al.
(author)
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Regulatory T cells control endothelial chemokine production and migration of T cells into intestinal tumors of APC(min/+) mice
- 2018
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In: Cancer Immunology Immunotherapy. - : Springer Science and Business Media LLC. - 0340-7004 .- 1432-0851. ; 67:7, s. 1067-1077
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Journal article (peer-reviewed)abstract
- Tumor-infiltrating lymphocytes are crucial for anti-tumor immunity. We have previously shown that regulatory T cells (Treg) are able to reduce T-cell transendothelial migration in vitro and accumulation of effector T cells in intestinal tumors in vivo. Treg depletion also resulted in increased levels of the chemokines CXCL9 and CXCL10 specifically in the tumors. In this study, we investigated the mechanisms for Treg mediated suppression of T-cell migration into intestinal tumors in the APC(min/+) mouse model. By breeding APC(min/+) mice with DEREG mice, which harbour a high affinity diphtheria toxin receptor under the control of the FOXP3 promoter, we were able to deplete Treg in tumor-bearing mice. Using adoptive transfer experiments, we could document a markedly increased migration of T cells specifically into Treg depleted tumors, and that Treg depletion results in increased production of the CXCR3 ligand CXCL10 from endothelial cells in the tumors. Furthermore, we were able to demonstrate that T cells use CXCR3 to migrate into intestinal tumors. In addition, human colon adenocarcinomas express high levels of mRNA CXCR3 ligands and tumor endothelial cells produce CXCL9 and CXCL10 ex vivo. In conclusion, this study demonstrates that Treg reduce endothelial CXCL10 production, inhibit T-cell migration into tumors and that CXCR3 mediated signalling is crucial for lymphocyte accumulation in intestinal tumors. Thus, immunotherapy aimed at Treg depletion may be effective by increasing not only T effector cell activity, but also their accumulation in tumors.
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| 4. |
- Akeus, Paulina, et al.
(author)
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Regulatory T cells reduce endothelial neutral sphingomyelinase 2 to prevent T-cell migration into tumors
- 2021
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In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 51:9, s. 2317-2329
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Journal article (peer-reviewed)abstract
- Endothelial cells are key regulators of transendothelial migration and their secretion of chemokines and expression of adhesion molecules facilitates lymphocyte entry into tissues. Previously, we demonstrated that Tregs can reduce transendothelial migration of T cells into tumors by decreasing endothelial CXCL10 secretion, but the mechanism by which this occurs is still not known. In this study, we aimed to define how Tregs decrease transendothelial migration into tumors. mRNA sequencing of intestinal tumor endothelial cells from Treg depleted mice identified neutral sphingomyelinase 2 (nSMase2) as a gene downregulated in the presence of Tregs. nSMase2 is expressed in human umbilical vein endothelial cells (HUVECs) and was decreased after coculture with Tregs. Furthermore, blocking of nSMase2 activity in vitro decreased VCAM1, CX3CL1, and CXCL10 expression in HUVECs, mirroring the same decrease found in Treg cocultures. In the APC(min/+) mouse model of intestinal cancer, nSMase2 is lower in tumor endothelial cells than in unaffected small intestine and chronic treatment with a nSMase2 inhibitor suppressed the increased migration that is otherwise seen in the absence of Tregs. We conclude that nSMase2 is an important mediator in endothelial cells supporting transendothelial migration, which may be targeted by Tregs to reduce T-cell migration into tumors.
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| 5. |
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| 6. |
- Albrecht, James W., et al.
(author)
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Career interruption and subsequent earnings : a reexamination using Swedish data
- 1996
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Reports (other academic/artistic)abstract
- This paper reexamines the link between career interruptions and subsequent wages. Using a rich new Swedish dataset, we are able to disaggregate time out of work into several components. Regressing log wages on aggregate total time out leads to the standard result, i.e., a negative coefficient on time out. However, we find that different types of time out have different effects on wages and that these effects vary by gender. This casts doubt on the usual human capital depreciation interpretation that has been placed on the negative coefficient of total time out in the wage equation. We propose a simple signaling model as an alternative interpretation.
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| 7. |
- Albrecht, James W., et al.
(author)
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Career interruption and subsequent earnings : A reexamination using Swedish data
- 1999
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In: Journal of Human Resources. ; 34, s. 294-311
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Journal article (peer-reviewed)abstract
- This paper reexamines the link between career interruptions and subsequent wages. Using a rich new Swedish dataset, we are able to disaggregate time out of work into several components. Regressing log wages on aggregate total time out leads to the standar
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| 8. |
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| 9. |
- Andersson Joona, Pernilla, et al.
(author)
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Etableringsreformens effekter på integrationen av nyanlända
- 2017
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In: Arbetsmarknad & Arbetsliv. - Karlstad : Karlstads universitet. - 1400-9692 .- 2002-343X. ; 23:1, s. 25-43
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Journal article (peer-reviewed)abstract
- Etableringsreformen genomfördes under 2010 av den förra regeringen för att underlätta och påskynda integrationen av nyanlända flyktingar och deras anhöriga. Reformen innebar att ansvaret för de nyanländas etablering överfördes från kommunerna till Arbetsförmedlingen. I den här artikeln analyserar vi reformens effekter på de nyanländas sysselsättning, löneinkomster och deltagande i utbildning ett, två och tre år efter beviljat uppehållstillstånd på basis av registerdata från SCB över samtliga nyanlända.
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| 10. |
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