학술논문
Interleukin-23 receptor signaling impairs the stability and function of colonic regulatory T cells
Document Type
article
Author
Justin Jacobse; Rachel E. Brown; Jing Li; Jennifer M. Pilat; Ly Pham; Sarah P. Short; Christopher T. Peek; Andrea Rolong; M. Kay Washington; Ruben Martinez-Barricarte; Mariana X. Byndloss; Catherine Shelton; Janet G. Markle; Yvonne L. Latour; Margaret M. Allaman; James E. Cassat; Keith T. Wilson; Yash A. Choksi; Christopher S. Williams; Ken S. Lau; Charles R. Flynn; Jean-Laurent Casanova; Edmond H.H.M. Rings; Janneke N. Samsom; Jeremy A. Goettel
Source
Cell Reports, Vol 42, Iss 2, Pp 112128- (2023)
Subject
Language
English
ISSN
2211-1247
Abstract
Summary: 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.