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Innate ??T17 cells play a protective role in DSS-induced colitis via recruitment of Gr-1+CD11b+ myeloid suppressor cells #MMPMID28638741
Sun X; Cai Y; Fleming C; Tong Z; Wang Z; Ding C; Qu M; Zhang Hg; Suo J; Yan J
Oncoimmunology 2017[]; 6 (5): ä PMID28638741show ga
Innate ?? T cells play critical roles in mucosal immunity such as regulating intestinal epithelial homeostasis. In addition, ?? T cells are significantly increased in the inflamed mucosa of patients with ulcerative colitis. However, ?? T cells are a heterogeneous population. IL-17-producing versus IFN?-producing ?? T cells play differential roles in different disease settings. Therefore, dissecting the exact role of different subsets of ?? T cells in colitis is essential for understanding colitis immunopathogenesis. In the current study, we found that TCR ?-deficient mice had a more severe dextran sodium sulfate (DSS)-induced colitis that was reduced upon reconstitution of ??T17 cells but not IFN?-producing ?? T cells. Immunophenotyping of the cellular infiltrate upon DSS-induced colitis showed a reduced infiltration of Gr-1+CD11b+ myeloid cells into the sites of inflammation in mice lacking ??T17 cells. Further experiments demonstrated that IL-17, IL-18, and chemokine CXCL5 were critical in Gr-1+CD11b+ myeloid cell recruitment. In vitro T cell suppressive assay indicated that this Gr-1+CD11b+ population was immunosuppressive. Depletion of Gr-1+CD11b+ myeloid cells resulted in an increase severity of DSS-induced colitis. Our study elucidates a new immune pathway involving ??T17-dependent recruitment of Gr-1+CD11b+ myeloid cells to the site of colitis inflammation important in the protection of colitis initiation and progression.