| First Author | Osman A | Year | 2021 |
| Journal | Nat Immunol | Volume | 22 |
| Issue | 9 | Pages | 1152-1162 |
| PubMed ID | 34385712 | Mgi Jnum | J:308663 |
| Mgi Id | MGI:6740259 | Doi | 10.1038/s41590-021-00987-1 |
| Citation | Osman A, et al. (2021) TCF-1 controls Treg cell functions that regulate inflammation, CD8(+) T cell cytotoxicity and severity of colon cancer. Nat Immunol |
| abstractText | The transcription factor TCF-1 is essential for the development and function of regulatory T (Treg) cells; however, its function is poorly understood. Here, we show that TCF-1 primarily suppresses transcription of genes that are co-bound by Foxp3. Single-cell RNA-sequencing analysis identified effector memory T cells and central memory Treg cells with differential expression of Klf2 and memory and activation markers. TCF-1 deficiency did not change the core Treg cell transcriptional signature, but promoted alternative signaling pathways whereby Treg cells became activated and gained gut-homing properties and characteristics of the TH17 subset of helper T cells. TCF-1-deficient Treg cells strongly suppressed T cell proliferation and cytotoxicity, but were compromised in controlling CD4(+) T cell polarization and inflammation. In mice with polyposis, Treg cell-specific TCF-1 deficiency promoted tumor growth. Consistently, tumor-infiltrating Treg cells of patients with colorectal cancer showed lower TCF-1 expression and increased TH17 expression signatures compared to adjacent normal tissue and circulating T cells. Thus, Treg cell-specific TCF-1 expression differentially regulates TH17-mediated inflammation and T cell cytotoxicity, and can determine colorectal cancer outcome. |
