| First Author | Paustian AMS | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 8 | Pages | e0182841 |
| PubMed ID | 28792532 | Mgi Jnum | J:248336 |
| Mgi Id | MGI:5919391 | Doi | 10.1371/journal.pone.0182841 |
| Citation | Paustian AMS, et al. (2017) Continuous IL-23 stimulation drives ILC3 depletion in the upper GI tract and, in combination with TNFalpha, induces robust activation and a phenotypic switch of ILC3. PLoS One 12(8):e0182841 |
| abstractText | Mutations in the Interleukin (IL)-23/IL-23 receptor loci are associated with increased inflammatory bowel disease (IBD) susceptibility, and IL-23 neutralization has shown efficacy in early clinical trials. To better understand how an excess of IL-23 affects the gastrointestinal tract, we investigated chronic systemic IL-23 exposure in healthy wildtype mice. As expected, IL-23 exposure resulted in early activation of intestinal type 3 innate lymphoid cells (ILC3), followed by infiltration of activated RORgammat+ T helper cells. Surprisingly, however, sustained IL-23 stimulus also dramatically reduced classical ILC3 populations within the proximal small intestine, and a phenotypically distinct T-bet expressing ILC3 population emerged. TNFalpha neutralization, a widely used IBD therapy, reduced several aspects of the IL-23 driven ILC3 response, suggesting a synergy between IL-23 and TNFalpha in ILC3 activation. In vitro studies supported these findings, revealing previously unappreciated effects of IL-23 and TNFalpha within the intestine. |
