TCF-1 controls Treg functions that regulate inflammation, CD8 T-cell cytotoxicity, and severity of colon cancer

Abstract The transcription factor TCF-1 is essential for the development and function of T regulatory (Treg) cells, however its poorly understood. Here, we show that primarily suppresses genes are co-bound by Foxp3. Single-cell RNA-seq analysis identified effector- central-memory Treg-cells with differential expression Klf2 memory activation markers. deficiency did not change core Treg transcriptional signature, but promoted alternative signaling pathways whereby became activated gained gut-homing TH17 characteristics. TCF-1-deficient strongly suppressed T-cell proliferation cytotoxicity, were compromised in controlling CD4+ polarization inflammation. In mice polyposis, cell-specific tumor growth. Consistently, tumor-infiltrating cells colorectal cancer patients showed lower increased signatures compared to adjacent normal tissue circulating T-cells. Thus, differentially regulates TH17-mediated inflammation can determine outcome. Supported NIH R01 AI 108682 (FG & KK), RO1 147652 (FG), R35GM138283 (MK), Praespero Innovation Award Alberta, Canada KK)