| First Author | Bhatt B | Year | 2018 |
| Journal | J Immunol | Volume | 200 |
| Issue | 8 | Pages | 2905-2914 |
| PubMed ID | 29514953 | Mgi Jnum | J:261310 |
| Mgi Id | MGI:6151827 | Doi | 10.4049/jimmunol.1701625 |
| Citation | Bhatt B, et al. (2018) Gpr109a Limits Microbiota-Induced IL-23 Production To Constrain ILC3-Mediated Colonic Inflammation. J Immunol 200(8):2905-2914 |
| abstractText | A set of coordinated interactions between gut microbiota and the immune cells surveilling the intestine play a key role in shaping local immune responses and intestinal health. Gpr109a is a G protein-coupled receptor expressed at a very high level on innate immune cells and previously shown to play a key role in the induction of colonic regulatory T cells. In this study, we show that Gpr109a(-/-)Rag1(-/-) mice exhibit spontaneous rectal prolapse and colonic inflammation, characterized by the presence of an elevated number of IL-17-producing Rorgammat(+) innate lymphoid cells (ILCs; ILC3). Genetic deletion of Rorgammat alleviated the spontaneous colonic inflammation in Gpr109a(-/-)Rag1(-/-) mice. Gpr109a-deficient colonic dendritic cells produce higher amounts of IL-23 and thereby promote ILC3. Moreover, the depletion of gut microbiota by antibiotics treatment decreased IL-23 production, ILC3, and colonic inflammation in Gpr109a(-/-)Rag1(-/-) mice. The ceca of Gpr109a(-/-)Rag1(-/-) mice showed significantly increased colonization by members of Bacteroidaceae, Porphyromonadaceae, Prevotellaceae, Streptococcaceae, Christensenellaceae, and Mogibacteriaceae, as well as IBD-associated microbiota such as Enterobacteriaceae and Mycoplasmataceae, compared with Rag1(-/-) mice, housed in a facility positive for Helicobacter and murine norovirus. Niacin, a Gpr109a agonist, suppressed both IL-23 production by colonic DCs and ILC3 number in a Gpr109a-dependent manner. Collectively, our data present a model suggesting that targeting Gpr109a will be potentially beneficial in the suppression of IL-23-mediated immunopathologies. |
