Abstract
Transforming growth factor β (TGF-β) represents a well-established signal required for tissue-resident memory T cell (TRM) formation at intestinal surfaces, regulating the expression of a large collection of genes coordinately promoting intestinal TRM differentiation. The functional contribution from each TGF-β-controlled transcription factor is not entirely known. Here, we find that TGF-β-induced T-bet downregulation and Hic1 induction represent two critical events during intestinal TRM differentiation. Importantly, T-bet deficiency significantly rescues intestinal TRM formation in the absence of the TGF-β receptor. Hic1 induction further strengthens TRM maturation in the absence of TGF-β and T-bet. Our results reveal that provision of certain TGF-β-induced molecular events can partially replace TGF-β signaling to promote the establishment of intestinal TRMs, which allows the functional dissection of TGF-β-induced transcriptional targets and molecular mechanisms for TRM differentiation.