| First Author | Pawlak M | Year | 2022 |
| Journal | Immunity | Volume | 55 |
| Issue | 9 | Pages | 1663-1679.e6 |
| PubMed ID | 36070768 | Mgi Jnum | J:336708 |
| Mgi Id | MGI:7345404 | Doi | 10.1016/j.immuni.2022.08.007 |
| Citation | Pawlak M, et al. (2022) Induction of a colitogenic phenotype in Th1-like cells depends on interleukin-23 receptor signaling. Immunity 55(9):1663-1679.e6 |
| abstractText | Interleukin-23 receptor plays a critical role in inducing inflammation and autoimmunity. Here, we report that Th1-like cells differentiated in vitro with IL-12 + IL-21 showed similar IL-23R expression to that of pathogenic Th17 cells using eGFP reporter mice. Fate mapping established that these cells did not transition through a Th17 cell state prior to becoming Th1-like cells, and we observed their emergence in vivo in the T cell adoptive transfer colitis model. Using IL-23R-deficient Th1-like cells, we demonstrated that IL-23R was required for the development of a highly colitogenic phenotype. Single-cell RNA sequencing analysis of intestinal T cells identified IL-23R-dependent genes in Th1-like cells that differed from those expressed in Th17 cells. The perturbation of one of these regulators (CD160) in Th1-like cells inhibited the induction of colitis. We thus uncouple IL-23R as a purely Th17 cell-specific factor and implicate IL-23R signaling as a pathogenic driver in Th1-like cells inducing tissue inflammation. |
