Induction of a colitogenic phenotype in Th1 cells depends on IL-23R signaling
Pawlak, M.; DeTomaso, D.; Meyer zu Horste, G.; Lee, Y.; Nyman, J.; Dionne, D.; Wang, C.; Wallrapp, A.; Burkett, P. R.; Riesenfeld, S. J.; Anderson, A. C.; Regev, A.; Xavier, R. J.; Yosef, N.; Kuchroo, V. K.
Show abstract
The cytokine receptor IL-23R plays a fundamental role in inflammation and autoimmunity. However, several observations have been difficult to reconcile under the assumption that only Th17 cells critically depend on IL-23 to acquire a pathogenic phenotype. Here, we report that Th1 cells differentiated in vitro with IL-12 + IL-21 show similar levels of IL-23R expression as in pathogenic Th17 cells. We demonstrate that IL-23R is required for Th1 cells to acquire a highly colitogenic phenotype. scRNAseq analysis of intestinal T cells enabled us to identify novel regulators induced by IL-23R-signaling in Th1 cells which differed from those expressed in Th17 cells. The perturbation of one of these regulators (CD160) in Th1 cells inhibited induction of colitis. In this process, we were able to uncouple IL-23R as a purely Th17 cell-specific factor and implicate IL-23R signaling as a pathogenic driver of Th1 cell-mediated tissue inflammation and disease.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Neurotrophic factor Neuritin modulates T cell electrical and metabolic state for the balance of tolerance and immunity 96%
- Enkephalin-mediated modulation of basal somatic sensitivity by regulatory T cells in mice 96%
- Pyroptosis-dependent and -independent cross-priming of CD8+ T cells by intestinal epithelial cell-derived antigen 95%
Similar papers in this journal
- Redundant cytokine requirement for intestinal microbiota-induced Th17 cell differentiation in draining lymph nodes 96%
- Lysophosphatidic acid-mediated GPR35 signaling in CX3CR1+ macrophages regulates the intestinal cytokine milieu 96%
- An essential role for miR-15/16 in Treg suppression and restriction of proliferation 95%
Similar papers in this journal
- Epithelial antigen presentation controls commensal-specific intraepithelial T-cells in the gut 96%
- Spatiotemporal single cell transcriptomic analyzis of human gut macrophages revealsmultiple functional and niche-specific subsets 96%
- Transcriptome profiling of pathogen-specific CD4 T cells identifies T-cell-intrinsic caspase-1 as an important regulator of Th17 differentiation 95%
Similar papers in this journal
- Multiple environmental signaling pathways control the differentiation of RORγt-expressing regulatory T cells 97%
- Sustained post-developmental T-bet expression is critical for the maintenance of type 1 innate lymphoid cells in vivo 96%
- Selective ablation of thymic and peripheral Foxp3+ regulatory T cell development 95%
Similar papers in this journal
- RTF1 mediates epigenetic control of Th17 cell differentiation via H2B monoubiquitination 96%
- Mitochondrial Fatty Acid Synthesis and Mecr Regulate CD4+ T Cell Function and Oxidative Metabolism 95%
- Mucosal vaccine adjuvant cyclic di-GMP differentiates lung moDCs into Bcl6+ and Bcl6- mature moDCs to induce lung memory CD4+ TH cells and lung TFH cells respectively 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.