2026-06-07T23:48:52Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/921862024-01-11T02:43:42Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Valle Noguera, Ana author Sancho Temiño, Lucía author Castillo González, Raquel author Villa Gómez, Cristina author Gomez Sánchez, María José author Ochoa Ramos, Anne author González Granado, José María author Cruz Adalia, Aranzazu 2024-01-10T09:52:46Z 2024-01-10T09:52:46Z 2023-12-26 Valle-Noguera A, Sancho-Temiño L, Castillo-González R, Villa-Gómez C, Gomez-Sánchez MJ, Ochoa-Ramos A, Yagüe-Fernández P, Soler Palacios B, Zorita V, Raposo-Ponce B, González-Granado JM, Aragonés J, Cruz-Adalia A. IL-18-induced HIF-1α in ILC3s ameliorates the inflammation of C. rodentium-induced colitis. Cell Rep. 2023 Dec 26;42(12):113508. doi: 10.1016/j.celrep.2023.113508. Epub 2023 Nov 28. PMID: 38019650. 2211-1247 10.1016/j.celrep.2023.113508 https://hdl.handle.net/20.500.14352/92186 https://www.sciencedirect.com/journal/cell-reports 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. eng Attribution-NonCommercial-NoDerivatives 4.0 International IL-18-induced HIF-1α in ILC3s ameliorates the inflammation of C. rodentium-induced colitis journal article 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URL https://docta.ucm.es/bitstreams/8b0a24ce-7b4a-4e08-b77d-5586ccf4a918/download File MD5 80653bb1fefa0ffe6161e37dd15278ec 11414713 application/pdf mmc2-2.pdf