RT Journal Article
T1 IL-18-induced HIF-1α in ILC3s ameliorates the inflammation of C. rodentium-induced colitis
A1 Valle Noguera, Ana
A1 Sancho Temiño, Lucía
A1 Castillo González, Raquel
A1 Villa Gómez, Cristina
A1 Gomez Sánchez, María José
A1 Ochoa Ramos, Anne
A1 González Granado, José María
A1 Cruz Adalia, Aranzazu
AB 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.
PB Cell Press
SN 2211-1247
YR 2023
FD 2023-12-26
LK https://hdl.handle.net/20.500.14352/92186
UL https://hdl.handle.net/20.500.14352/92186
LA eng
NO 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.
NO Ministerio de Ciencia e Innovación
NO Instituto de Salud Carlos III (ISCIII)
NO European Regional Development Fund
DS Docta Complutense
RD 6 oct 2024