IL-18-induced HIF-1α in ILC3s ameliorates the inflammation of C. rodentium-induced colitis
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 gov- erning HIF-1a in ILC3s and other innate RORgt+ cells during in vivo infections are...
| Autores: | , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universidad Complutense de Madrid (UCM) |
| Repositorio: | Docta Complutense |
| Idioma: | inglés |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/92186 |
| Acceso en línea: | https://hdl.handle.net/20.500.14352/92186 |
| Access Level: | acceso abierto |
| Palabra clave: | 612.017 CP: Immunology Citrobacter rodentium HIF-1α IL-18 IL-22 TLR2 colitis group 3 innate lymphoid cells infection innate RORγt(+) cells Inmunología 2412.99 Otras |
| Sumario: | 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 gov- erning HIF-1a in ILC3s and other innate RORgt+ cells during in vivo infections are poorly understood. In our study, transgenic mice with specific Hif-1a gene inactivation in innate RORgt+ cells (RAG1KO HIF- 1a6Rorc) exhibit more severe colitis following Citrobacter rodentium infection, primarily due to the inability to upregulate IL-22. We find that HIF-1a6Rorc mice have impaired IL-22 production in ILC3s, while non- ILC3 innate RORgt+ 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-1a, 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-1a in ILC3s, which is crucial for protection against this pathogen. |
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