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Tcf1 controls Treg functions that regulate inflammation, CD8 T-cell cytotoxicity, and severity of colon cancer

ABSTRACT: Tcf1, the DNA-binding partner of β-catenin, is essential for the development and function of T regulatory cells (Tregs). However, how Tcf1 regulates Treg functional specification is less understood. Here, we ablated Tcf1 in Tregs to elucidate its role in Treg specification in healthy mice and mice with colon cancer. RNAseq and single-cell RNAseq revealed that Tcf1 deficient Tregs maintain their core transcriptional signature and diversity, but promote T-cell receptor, Tgfβ receptor, TH17, and Wnt/β-catenin signaling pathways. Central-memory-Tregs with low Klf2 and effector-Tregs with high Mif expression gain TH17 characteristics and mature into effector Treg subpopulations that strongly express cMaf. Tcf1 deficient Tregs exhibit enhanced suppression of T-cell proliferation and cytotoxicity but are compromised in controlling CD4+ T-cell polarization and inflammation. In mice with polyposis, Tcf1 deficient Tregs promote inflammation and tumor growth. Thus, Tcf1 determines Treg functions that regulate TH17 inflammation and the course and outcome of colorectal cancer.

ORGANISM(S): Mus musculus

PROVIDER: GSE163084 | GEO | 2021/06/01

REPOSITORIES: GEO

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