title: 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-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 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-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(+)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.
authors.affiliation: Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, Chiba, Japan ; Laboratory for Epithelial Immunobiology, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Kanagawa, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Mandai
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takahashi
authors.forename: Koji
authors.initials: K
authors.lastname: Hase
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Obata
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Furusawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Ebisawa
authors.forename: Tomoo
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Toru
authors.initials: T
authors.lastname: Sato
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Katsuno
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimaoka
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
authors.forename: Kotaro
authors.initials: K
authors.lastname: Yokote
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohno
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D002908:Chronic Disease; D003092:Colitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008875:Middle Aged; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D055815:Young Adult
chemical_list: C106330:CXCR6 protein, human; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D011991:Receptors, Virus