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

ABSTRACT

Innate γδ T cells play critical roles in mucosal immunity such as regulating intestinal epithelial homeostasis. In addition, γδ T cells are significantly increased in the inflamed mucosa of patients with ulcerative colitis. However, γδ T cells are a heterogeneous population. IL-17-producing versus IFNγ-producing γδ T cells play differential roles in different disease settings. Therefore, dissecting the exact role of different subsets of γδ T cells in colitis is essential for understanding colitis immunopathogenesis. In the current study, we found that TCR δ-deficient mice had a more severe dextran sodium sulfate (DSS)-induced colitis that was reduced upon reconstitution of γδT17 cells but not IFNγ-producing γδ 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 γδT17 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 γδT17-dependent recruitment of Gr-1⁺CD11b⁺ myeloid cells to the site of colitis inflammation important in the protection of colitis initiation and progression.

KEYWORDS:

• γδ T cells
• colitis
• IL-17
• myeloid cells

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Funding

This work was partly supported by the NIH grant and the Kentucky Research Challenge Trust Fund. Huang-Ge Zhang is supported by a Research Career Scientist (RCS) Award.

Author contributions

X.S. participated in the design and coordination of the research project, collected, performed, and analyzed data, and contributed to manuscript writing. Y.H.C, C.F., Z.T., and C.D. participated in the design and coordination of the research project, collected, performed, and analyzed data. M.Y.Q participated in some supporting experiments for manuscript revision. C.F. contributed to manuscript writing. Z.W. reviewed and scored all histological slides. H.G.Z. participated in experimental design. J.S. and J.Y. participated in the design and coordination of the research project, supervised whole project, analyzed data, revised the manuscript and approved the final version of the manuscript.