Granzyme B prevents aberrant IL-17 production and intestinal pathogenicity in CD4+ T cells

Abstract

CD4 + T cell activation and differentiation are important events that set the stage for proper immune responses. Many factors are involved in the activation and differentiation of T cells, and these events are tightly controlled to prevent unwanted and/or exacerbated immune responses that may harm the host. It has been well-documented that granzyme B, a potent serine protease involved in cell-mediated cytotoxicity, is readily expressed by certain CD4 + T cells, such as regulatory T cells and CD4 + CD8αα + intestinal intraepithelial lymphocytes, both of which display cytotoxicity associated with granzyme B. However, because not all CD4 + T cells expressing granzyme B are cytotoxic, additional roles for this protease in CD4 + T cell biology remain unknown. Here, using a combination of in vivo and in vitro approaches, we report that granzyme B-deficient CD4 + T cells display increased IL-17 production. In the adoptive transfer model of intestinal inflammation, granzyme B-deficient CD4 + T cells triggered a more rapid disease onset than their WT counterparts, and presented a differential transcription profile. Similar results were also observed in granzyme B-deficient mice infected with Citrobacter rodentium. Our results suggest that granzyme B modulates CD4 + T cell differentiation, providing a new perspective into the biology of this enzyme.

Part of CIRS Nexus · Curated by Lauren Lowenstein, The Biotoxin Lady

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