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oai:docta.ucm.es:20.500.14352/921862024-01-11T02:43:42Zcom_20.500.14352_14col_20.500.14352_15

IL-18-induced HIF-1α in ILC3s ameliorates the inflammation of C. rodentium-induced colitis Valle Noguera, Ana Sancho Temiño, Lucía Castillo González, Raquel Villa Gómez, Cristina Gomez Sánchez, María José Ochoa Ramos, Anne González Granado, José María Cruz Adalia, Aranzazu 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. 2024-01-10T09:52:46Z 2024-01-10T09:52:46Z 2024-01-10T09:52:46Z 2023-12-26 journal article https://hdl.handle.net/20.500.14352/92186 2211-1247 10.1016/j.celrep.2023.113508 eng info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-093647-B-I00/ES/CONTROL DE LA REGULACION METABOLICA Y MOLECULAR MEDIADA POR HIF-1A EN LAS CELULAS INNATAS LINFOIDES/ PID2021-122780OB-I00 CNS2022-135365 info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F00306/ES/INMUNOLOGIA, INMUNOPATOLOGIA Y TERAPIA EN ENFERMEDAD INFLAMATORIA INTESTINAL/ 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. http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 International Cell Press