Transcription factor TCF1 binds to RORγt and orchestrates a regulatory network that determines homeostatic Th17 cell state.

ABSTRACT: T helper (Th) 17 cells encompass a spectrum of cell states, including cells that maintain homeostatic tissue functions and pro-inflammatory cells that can drive autoimmune tissue damage. Identifying regulators that determine Th17 cell states can identify ways to control tissue inflammation and restore homeostasis. Here, we found that interleukin (IL)-23, a cytokine critical for inducing pro-inflammatory Th17 cells, decreased transcription factor T cell factor 1 (TCF1) expression. Conditional deletion of TCF1 in mature T cells increased the pro-inflammatory potential of Th17 cells, even in the absence of IL-23 receptor signaling, and conferred pro-inflammatory potential to homeostatic Th17 cells. Conversely, sustained TCF1 expression decreased pro-inflammatory Th17 potential. Mechanisticall

SUBMITTER: Mangani D 

PROVIDER: S-EPMC11614491 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature