| First Author | Valle-Noguera A | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 12 | Pages | 113508 |
| PubMed ID | 38019650 | Mgi Jnum | J:343541 |
| Mgi Id | MGI:7567245 | Doi | 10.1016/j.celrep.2023.113508 |
| Citation | Valle-Noguera A, et al. (2023) IL-18-induced HIF-1alpha in ILC3s ameliorates the inflammation of C. rodentium-induced colitis. Cell Rep 42(12):113508 |
| abstractText | Group 3 innate lymphoid cells (ILC3s) are vital for defending tissue barriers from invading pathogens. Hypoxia influences the production of intestinal ILC3-derived cytokines by activating HIF. Yet, the mechanisms governing HIF-1alpha in ILC3s and other innate RORgammat(+) cells during in vivo infections are poorly understood. In our study, transgenic mice with specific Hif-1a gene inactivation in innate RORgammat(+) cells (RAG1KO HIF-1alpha(triangle upRorc)) exhibit more severe colitis following Citrobacter rodentium infection, primarily due to the inability to upregulate IL-22. We find that HIF-1alpha(triangle upRorc) mice have impaired IL-22 production in ILC3s, while non-ILC3 innate RORgammat(+) cells, also capable of producing IL-22, remain unaffected. Furthermore, we show that IL-18, induced by Toll-like receptor 2, selectively triggers IL-22 in ILC3s by transcriptionally upregulating HIF-1alpha, revealing an oxygen-independent regulatory pathway. Our results highlight that, during late-stage C. rodentium infection, IL-18 induction in the colon promotes IL-22 through HIF-1alpha in ILC3s, which is crucial for protection against this pathogen. |
