2026-04-29T19:34:51Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/192732024-09-27T07:58:31Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc 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 Yagüe-Fernández, Patricia author Soler Palacios, Blanca author Zorita, Virginia author Raposo-Ponce, Berta author González-Granado, José María author Aragonés, Julián author Cruz-Adalia, Aránzazu author 2023-12-26 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-1α in ILC3s and other innate RORγt+ cells during in vivo infections are poorly understood. In our study, transgenic mice with specific Hif-1a gene inactivation in innate RORγt+ cells (RAG1KO HIF-1α▵Rorc) exhibit more severe colitis following Citrobacter rodentium infection, primarily due to the inability to upregulate IL-22. We find that HIF-1α▵Rorc mice have impaired IL-22 production in ILC3s, while non-ILC3 innate RORγt+ 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-1α, 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-1α in ILC3s, which is crucial for protection against this pathogen. Cell Rep. 2023 Dec 26;42(12):113508. 10.1016/j.celrep.2023.113508 2211-1247 Cell reports 38019650 http://hdl.handle.net/20.500.12105/19273 IL-18-induced HIF-1α in ILC3s ameliorates the inflammation of C. rodentium-induced colitis.