Journal article
Interleukin-23 receptor signaling impairs the stability and function of colonic regulatory T cells
Cell reports (Cambridge), Vol.42(2), pp.112128-112128
02/28/2023
DOI: 10.1016/j.celrep.2023.112128
PMCID: PMC10432575
PMID: 36807140
Abstract
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.
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•Studying IL-23R signaling in Tregs requires a focus on intestinal Tregs•IL-23R-deficient Tregs have a cell-intrinsic advantage over IL-23R-sufficient Tregs•IL-23R-signaling increases apoptosis in intestinal Tregs•Cholesterol homeostasis is altered in IL-23R-deficient colonic Tregs
Jacobse et al. show the cytokine interleukin-23 specifically negatively regulates suppressive function and survival of intestinal regulatory T cells in mice.
Details
- Title: Subtitle
- Interleukin-23 receptor signaling impairs the stability and function of colonic regulatory T cells
- Creators
- Justin Jacobse - Vanderbilt University Medical CenterRachel E. Brown - Vanderbilt University School of MedicineJing Li - Vanderbilt University Medical CenterJennifer M. Pilat - Vanderbilt University School of MedicineLy Pham - Vanderbilt University Medical CenterSarah P. Short - Vanderbilt University Medical CenterChristopher T. Peek - Vanderbilt University Medical CenterAndrea Rolong - Vanderbilt University School of MedicineM. Kay Washington - Vanderbilt University Medical CenterRuben Martinez-Barricarte - Vanderbilt University Medical CenterMariana X. Byndloss - Vanderbilt University Medical CenterCatherine Shelton - Vanderbilt University Medical CenterJanet G. Markle - Vanderbilt University Medical CenterYvonne L. Latour - Vanderbilt University Medical CenterMargaret M. Allaman - Vanderbilt University Medical CenterJames E. Cassat - Vanderbilt University Medical CenterKeith T. Wilson - Vanderbilt University Medical CenterYash A. Choksi - Vanderbilt University Medical CenterChristopher S. Williams - Vanderbilt University Medical CenterKen S. Lau - Vanderbilt University Medical CenterCharles R. Flynn - Vanderbilt University Medical CenterJean-Laurent Casanova - Rockefeller UniversityEdmond H.H.M. Rings - Leiden University Medical CenterJanneke N. Samsom - Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center, Rotterdam, the NetherlandsJeremy A. Goettel - Vanderbilt University Medical Center
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.42(2), pp.112128-112128
- DOI
- 10.1016/j.celrep.2023.112128
- PMID
- 36807140
- PMCID
- PMC10432575
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 02/28/2023
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984420942002771
Metrics
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