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

Yasushi Mandai, Daisuke Takahashi, Koji Hase, Yuuki Obata, Yukihiro Furusawa, Masashi Ebisawa, Tomoo Nakagawa, Toru Sato, Tatsuro Katsuno, Yasushi Saito, Takeshi Shimaoka, Osamu Yokosuka, Kotaro Yokote, Hiroshi Ohno

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7 Citations (Scopus)

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-γ and TNF-α. 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 CXCR6- CD4+ T-cell subsets consist of the cells with effector and effector-memory cells, the more cells in the CXCR6+ subset produced IFN-γ and TNF-α 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+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 CXCR6-CD4+ T-cell subset serves as a colitogenic memory compartment that retains the ability to proliferate and differentiate into CXCR6+CD4+ T cells.

Original languageEnglish
Article numbere65488
JournalPloS one
Volume8
Issue number6
DOIs
Publication statusPublished - 2013 Jun 19

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Mandai, Y., Takahashi, D., Hase, K., Obata, Y., Furusawa, Y., Ebisawa, M., Nakagawa, T., Sato, T., Katsuno, T., Saito, Y., Shimaoka, T., Yokosuka, O., Yokote, K., & Ohno, H. (2013). Distinct Roles for CXCR6+ and CXCR6- CD4+ T Cells in the Pathogenesis of Chronic Colitis. PloS one, 8(6), [e65488]. https://doi.org/10.1371/journal.pone.0065488