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Plos One : Distinct Roles for Cxcr6+ and Cxcr62 Cd4+ T Cells in the Pathogenesis of Chronic Colitis, Volume 8

By Mizoguchi, Emiko

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Book Id: WPLBN0003946911
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos One : Distinct Roles for Cxcr6+ and Cxcr62 Cd4+ T Cells in the Pathogenesis of Chronic Colitis, Volume 8  
Author: Mizoguchi, Emiko
Volume: Volume 8
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection (Contemporary)
Publication Date:
Publisher: Plos


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Mizoguchi, E. (n.d.). Plos One : Distinct Roles for Cxcr6+ and Cxcr62 Cd4+ T Cells in the Pathogenesis of Chronic Colitis, Volume 8. Retrieved from

Description : 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-c and TNF-a. 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 CD45RBhigh 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 CXCR62 CD4+ T-cell subsets consist of the cells with effector and effector-memory cells, the more cells in the CXCR6+ subset produced IFN-c and TNF-a compared to CXCR62 subset, and only the CXCR6+ subset produced IL-17A. Nevertheless, adoptive retransfer of lamina propria CXCR6+ T cells into Rag12/ 2 recipients failed to induce the disease due to limited expansion of the transferred cells. By contrast, retransfer of CXCR62 cells evoked colitis similar to that observed in CD4+CD45RBhigh 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 CXCR62CD4+ T-cell subset serves as a colitogenic memory compartment that retains the ability to proliferate and differentiate into CXCR6+CD4+ T cells.


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