| First Author | Jacobse J | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 2 | Pages | 112128 |
| PubMed ID | 36807140 | Mgi Jnum | J:343178 |
| Mgi Id | MGI:7564372 | Doi | 10.1016/j.celrep.2023.112128 |
| Citation | Jacobse J, et al. (2023) Interleukin-23 receptor signaling impairs the stability and function of colonic regulatory T cells. Cell Rep 42(2):112128 |
| abstractText | The cytokine interleukin-23 (IL-23) is involved in the pathogenesis of inflammatory and autoimmune conditions including inflammatory bowel disease (IBD). IL23R is enriched in intestinal Tregs, yet whether IL-23 modulates intestinal Tregs remains unknown. Here, investigating IL-23R signaling in Tregs specifically, we show that colonic Tregs highly express Il23r compared with Tregs from other compartments and their frequency is reduced upon IL-23 administration and impairs Treg suppressive function. Similarly, colonic Treg frequency is increased in mice lacking Il23r specifically in Tregs and exhibits a competitive advantage over IL-23R-sufficient Tregs during inflammation. Finally, IL-23 antagonizes liver X receptor pathway, cellular cholesterol transporter Abca1, and increases Treg apoptosis. Our results show that IL-23R signaling regulates intestinal Tregs by increasing cell turnover, antagonizing suppression, and decreasing cholesterol efflux. These results suggest that IL-23 negatively regulates Tregs in the intestine with potential implications for promoting chronic inflammation in patients with IBD. |
