Dataset Information


Distinct Roles for CXCR6(+) and CXCR6(-) CD4(+) T Cells in the Pathogenesis of Chronic Colitis.

ABSTRACT: CD4(+) T cells play a central role in the development of inflammatory bowel disease (IBD) via high-level production of effector cytokines such as IFN-? and TNF-?. To better characterize the colitogenic CD4(+) T cells, we examined their expression of CXCR6, a chemokine receptor that is expressed by T cells upon activation and is upregulated in several inflammatory diseases. We found that 80% of colonic lamina propria CD4(+) T cells expressed CXCR6 in the CD45RB(high) T cell-transferred colitis model. CXCR6 expression was similarly upregulated in inflamed mucosa of patients with Crohn's disease. Although surface marker analysis demonstrated that both CXCR6(+) and CXCR6(-) CD4(+) T-cell subsets consist of the cells with effector and effector-memory cells, the more cells in the CXCR6(+) subset produced IFN-? and TNF-? compared to CXCR6(-) subset, and only the CXCR6(+) subset produced IL-17A. Nevertheless, adoptive retransfer of lamina propria CXCR6(+) T cells into Rag1 (-/-) recipients failed to induce the disease due to limited expansion of the transferred cells. By contrast, retransfer of CXCR6(-) cells evoked colitis similar to that observed in CD4(+)CD45RB(high) T cell-transferred mice, and resulted in their conversion into CXCR6(+) cells. Collectively, these observations suggest that the CXCR6(+)CD4(+) T-cell subset consists of terminally differentiated effector cells that serve as the major source of effector cytokines in the inflamed tissue, whereas CXCR6(-)CD4(+) T-cell subset serves as a colitogenic memory compartment that retains the ability to proliferate and differentiate into CXCR6(+)CD4(+) T cells.


PROVIDER: S-EPMC3686755 | BioStudies | 2013-01-01

REPOSITORIES: biostudies

Similar Datasets

2018-01-01 | S-EPMC5919676 | BioStudies
2014-01-01 | S-EPMC4022635 | BioStudies
2013-01-01 | S-EPMC3896249 | BioStudies
2019-01-01 | S-EPMC6888981 | BioStudies
2013-04-09 | E-GEOD-45881 | ArrayExpress
2019-01-01 | S-EPMC6862482 | BioStudies
2019-01-01 | S-EPMC6416161 | BioStudies
2014-01-01 | S-EPMC3984212 | BioStudies
2020-01-01 | S-EPMC7549382 | BioStudies
2020-01-01 | S-EPMC7426740 | BioStudies