Innate γδT17 cells play a protective role in DSS-induced colitis via recruitment of Gr-1 + CD11b + myeloid suppressor cells.

Innate gamma delta T cells play critical roles in mucosal immunity such as regulating intestinal epithelial homeostasis. In addition, gamma delta T cells are significantly increased in the inflamed mucosa of patients with ulcerative colitis. However,gamma delta T cells are a heterogeneous population. IL-17-producing versus IFNg-producing gamma delta T cells play differential roles in different disease settings. Therefore, dissecting the exact role of different subsets of gamma delta T cells in colitis is essential for understanding colitis immunopathogenesis. In the current study, we found that TCR delta-deficient mice had a more severe dextran sodium sulfate (DSS)-induced colitis that was reduced upon reconstitution of gamma delta T17 cells but not IFN gamma-producing gamma delta 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 gamma delta 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-1CCD11bC 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 gamma delta T17-dependent recruitment of Gr-1(+)CD11b(+) myeloid cells to the site of colitis inflammation important in the protection of colitis initiation and progression.