Mouse CD8+ T cell subsets differentially generate IL-17-expressing cells in the colon epithelium and lamina propria

Colon-resident CD8+ T cells actively contribute to gut homeostasis and the pathogenesis of inflammatory bowel disease. However, their heterogeneity in generating IL-17-expressing CD8+ T cells, i.e. Tc17 cells, has not been thoroughly revealed. This study aims to characterize the abilities of mouse colonic intraepithelial (IE) and lamina propria (LP) CD8+ T cell subsets to differentiate into Tc17 cells. Using flow cytometry, we found that normal TCRβ+CD4-CD8αα+ cells (CD8αα T cells) and TCRβ+CD4-CD8αβ T cells, (CD8αβ T cells), either IE or LP, expressed abundant granzymes and IFN-γ but minute IL-17A. Under the in vitro Tc17-inducing condition, IE CD8αα T cells showed the weakest Tc17 differentiation ability and LP CD8αβ T cells exhibited the strongest Tc17 differentiation ability, whereas IE CD8αβ T cells and LP CD8αα T cells demonstrated moderate Tc17 differentiation abilities. The expression of IL-6 receptor, TGF-β receptor, TCR signaling indicators, CD161, and IL-23 receptor was low in IE CD8αα T cells, median in IE CD8αβ T cells and LP CD8αα T cells, but high in LP CD8αβ T cells. IE CD8αα T cells weakly induced the expression of chemokines, cytokines, and host defense mediators in colonic epithelial cells while LP CD8αβ T cells showed a robust up-regulatory effect. Furthermore, these colonic CD8+ T cell subsets also exhibited different abilities to generate Tc17 cells in inflamed colons. Collectively, LP CD8αβ T cells have the strongest Tc17 differentiation ability and might play a more significant role than the other subsets in Tc17-mediated immunity or inflammation in the colon.