Induction of a colitogenic phenotype in Th1-like cells depends on interleukin-23 receptor signaling

Immunity. 2022 Sep 13;55(9):1663-1679.e6. doi: 10.1016/j.immuni.2022.08.007. Epub 2022 Sep 6.


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.

Keywords: IL-23; IL-23 receptor; T helper cell; Th1-like cell; autoimmunity; colitis; inflammation; inflammatory bowel disease; pre-clinical mouse model; single-cell RNA sequencing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis*
  • Inflammation / metabolism
  • Interleukin-23 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Phenotype
  • Receptors, Interleukin* / genetics
  • Receptors, Interleukin* / metabolism
  • Th1 Cells
  • Th17 Cells


  • Interleukin-23
  • Receptors, Interleukin