IL-17RA-signaling in Lgr5⁺ intestinal stem cells induces expression of transcription factor ATOH1 to promote secretory cell lineage commitment.

ABSTRACT: The Th17 cell-lineage-defining cytokine IL-17A contributes to host defense and inflammatory disease by coordinating multicellular immune responses. The IL-17 receptor (IL-17RA) is expressed by diverse intestinal cell types, and therapies targeting IL-17A induce adverse intestinal events, suggesting additional tissue-specific functions. Here, we used multiple conditional deletion models to identify a role for IL-17A in secretory epithelial cell differentiation in the gut. Paneth, tuft, goblet, and enteroendocrine cell numbers were dependent on IL-17A-mediated induction of the transcription factor ATOH1 in Lgr5⁺ intestinal epithelial stem cells. Although dispensable at steady state, IL-17RA signaling in ATOH1⁺ cells was required to regenerate secretory cells following i

SUBMITTER: Lin X 

PROVIDER: S-EPMC8895883 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature