| First Author | Basu J | Year | 2021 |
| Journal | Nat Immunol | Volume | 22 |
| Issue | 8 | Pages | 969-982 |
| PubMed ID | 34312548 | Mgi Jnum | J:310191 |
| Mgi Id | MGI:6740266 | Doi | 10.1038/s41590-021-00980-8 |
| Citation | Basu J, et al. (2021) Essential role of a ThPOK autoregulatory loop in the maintenance of mature CD4(+) T cell identity and function. Nat Immunol 22(8):969-982 |
| abstractText | The transcription factor ThPOK (encoded by the Zbtb7b gene) controls homeostasis and differentiation of mature helper T cells, while opposing their differentiation to CD4(+) intraepithelial lymphocytes (IELs) in the intestinal mucosa. Thus CD4 IEL differentiation requires ThPOK transcriptional repression via reactivation of the ThPOK transcriptional silencer element (Sil(ThPOK)). In the present study, we describe a new autoregulatory loop whereby ThPOK binds to the Sil(ThPOK) to maintain its own long-term expression in CD4 T cells. Disruption of this loop in vivo prevents persistent ThPOK expression, leads to genome-wide changes in chromatin accessibility and derepresses the colonic regulatory T (Treg) cell gene expression signature. This promotes selective differentiation of naive CD4 T cells into GITR(lo)PD-1(lo)CD25(lo) (Triple(lo)) Treg cells and conversion to CD4(+) IELs in the gut, thereby providing dominant protection from colitis. Hence, the ThPOK autoregulatory loop represents a key mechanism to physiologically control ThPOK expression and T cell differentiation in the gut, with potential therapeutic relevance. |
