|  Help  |  About  |  Contact Us

Publication : Ornithine decarboxylase supports ILC3 responses in infectious and autoimmune colitis through positive regulation of IL-22 transcription.

First Author  Peng V Year  2022
Journal  Proc Natl Acad Sci U S A Volume  119
Issue  45 Pages  e2214900119
PubMed ID  36279426 Mgi Jnum  J:331529
Mgi Id  MGI:7386695 Doi  10.1073/pnas.2214900119
Citation  Peng V, et al. (2022) Ornithine decarboxylase supports ILC3 responses in infectious and autoimmune colitis through positive regulation of IL-22 transcription. Proc Natl Acad Sci U S A 119(45):e2214900119
abstractText  Group 3 innate lymphoid cells (ILC3s) are RORgammaT<sup>+</sup> lymphocytes that are predominately enriched in mucosal tissues and produce IL-22 and IL-17A. They are the innate counterparts of Th17 cells. While Th17 lymphocytes utilize unique metabolic pathways in their differentiation program, it is unknown whether ILC3s make similar metabolic adaptations. We employed single-cell RNA sequencing and metabolomic profiling of intestinal ILC subsets to identify an enrichment of polyamine biosynthesis in ILC3s, converging on the rate-limiting enzyme ornithine decarboxylase (ODC1). In vitro and in vivo studies demonstrated that exogenous supplementation with the polyamine putrescine or its biosynthetic substrate, ornithine, enhanced ILC3 production of IL-22. Conditional deletion of ODC1 in ILC3s impaired mouse antibacterial defense against <i>Citrobacter rodentium</i> infection, which was associated with a decrease in anti-microbial peptide production by the intestinal epithelium. Furthermore, in a model of anti-CD40 colitis, deficiency of ODC1 in ILC3s markedly reduced the production of IL-22 and severity of inflammatory colitis. We conclude that ILC3-intrinsic polyamine biosynthesis facilitates efficient defense against enteric pathogens as well as exacerbates autoimmune colitis, thus representing an attractive target to modulate ILC3 function in intestinal disease.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

9 Bio Entities

Trail: Publication

0 Expression