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; Yagüe-Fernández, Patricia; Soler Palacios, Blanca; Zorita, Virginia; Raposo-Ponce, Berta; González-Granado, José María; Aragonés, Julián; Cruz-Adalia, Aránzazu

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 governing HIF-1α in ILC3s and other innate RORγt+ cells during in vivo infections are p...

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Detalles Bibliográficos
Autores:	Valle-Noguera, Ana, Sancho-Temiño, Lucía, Castillo-González, Raquel, Villa-Gómez, Cristina, Gomez-Sánchez, María José, Ochoa-Ramos, Anne, Yagüe-Fernández, Patricia, Soler Palacios, Blanca, Zorita, Virginia, Raposo-Ponce, Berta, González-Granado, José María, Aragonés, Julián, Cruz-Adalia, Aránzazu
Tipo de recurso:	artículo
Fecha de publicación:	2023
País:	España
Institución:	Instituto de Salud Carlos III (ISCIII)
Repositorio:	Repisalud
Idioma:	inglés
OAI Identifier:	oai:repisalud.isciii.es:20.500.12105/19273
Acceso en línea:	http://hdl.handle.net/20.500.12105/19273
Access Level:	acceso abierto
Palabra clave:	Interleukins Colitis Mice Animals Immunity, Innate Nuclear Receptor Subfamily 1, Group F, Member 3 Lymphocytes Interleukin-18 Inflammation Mice, Transgenic Mice, Inbred C57BL

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spelling	IL-18-induced HIF-1α in ILC3s ameliorates the inflammation of C. rodentium-induced colitis.Valle-Noguera, AnaSancho-Temiño, LucíaCastillo-González, RaquelVilla-Gómez, CristinaGomez-Sánchez, María JoséOchoa-Ramos, AnneYagüe-Fernández, PatriciaSoler Palacios, BlancaZorita, VirginiaRaposo-Ponce, BertaGonzález-Granado, José MaríaAragonés, JuliánCruz-Adalia, AránzazuInterleukinsColitisMiceAnimalsImmunity, InnateNuclear Receptor Subfamily 1, Group F, Member 3LymphocytesInterleukin-18InflammationMice, TransgenicMice, Inbred C57BLGroup 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 PressMinisterio de Ciencia e Innovación (España)Instituto de Salud Carlos IIIComunidad de Madrid (España)Ministerio de Educación y Formación Profesional (España)20242024-05-0720232023-12-2620232023-12-26journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/19273reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/192732026-06-12T12:43:37Z
dc.title.none.fl_str_mv	IL-18-induced HIF-1α in ILC3s ameliorates the inflammation of C. rodentium-induced colitis.
title	IL-18-induced HIF-1α in ILC3s ameliorates the inflammation of C. rodentium-induced colitis.
spellingShingle	IL-18-induced HIF-1α in ILC3s ameliorates the inflammation of C. rodentium-induced colitis. Valle-Noguera, Ana Interleukins Colitis Mice Animals Immunity, Innate Nuclear Receptor Subfamily 1, Group F, Member 3 Lymphocytes Interleukin-18 Inflammation Mice, Transgenic Mice, Inbred C57BL
title_short	IL-18-induced HIF-1α in ILC3s ameliorates the inflammation of C. rodentium-induced colitis.
title_full	IL-18-induced HIF-1α in ILC3s ameliorates the inflammation of C. rodentium-induced colitis.
title_fullStr	IL-18-induced HIF-1α in ILC3s ameliorates the inflammation of C. rodentium-induced colitis.
title_full_unstemmed	IL-18-induced HIF-1α in ILC3s ameliorates the inflammation of C. rodentium-induced colitis.
title_sort	IL-18-induced HIF-1α in ILC3s ameliorates the inflammation of C. rodentium-induced colitis.
dc.creator.none.fl_str_mv	Valle-Noguera, Ana Sancho-Temiño, Lucía Castillo-González, Raquel Villa-Gómez, Cristina Gomez-Sánchez, María José Ochoa-Ramos, Anne Yagüe-Fernández, Patricia Soler Palacios, Blanca Zorita, Virginia Raposo-Ponce, Berta González-Granado, José María Aragonés, Julián Cruz-Adalia, Aránzazu
author	Valle-Noguera, Ana
author_facet	Valle-Noguera, Ana Sancho-Temiño, Lucía Castillo-González, Raquel Villa-Gómez, Cristina Gomez-Sánchez, María José Ochoa-Ramos, Anne Yagüe-Fernández, Patricia Soler Palacios, Blanca Zorita, Virginia Raposo-Ponce, Berta González-Granado, José María Aragonés, Julián Cruz-Adalia, Aránzazu
author_role	author
author2	Sancho-Temiño, Lucía Castillo-González, Raquel Villa-Gómez, Cristina Gomez-Sánchez, María José Ochoa-Ramos, Anne Yagüe-Fernández, Patricia Soler Palacios, Blanca Zorita, Virginia Raposo-Ponce, Berta González-Granado, José María Aragonés, Julián Cruz-Adalia, Aránzazu
author2_role	author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Ministerio de Ciencia e Innovación (España) Instituto de Salud Carlos III Comunidad de Madrid (España) Ministerio de Educación y Formación Profesional (España)
dc.subject.none.fl_str_mv	Interleukins Colitis Mice Animals Immunity, Innate Nuclear Receptor Subfamily 1, Group F, Member 3 Lymphocytes Interleukin-18 Inflammation Mice, Transgenic Mice, Inbred C57BL
topic	Interleukins Colitis Mice Animals Immunity, Innate Nuclear Receptor Subfamily 1, Group F, Member 3 Lymphocytes Interleukin-18 Inflammation Mice, Transgenic Mice, Inbred C57BL
description	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.
publishDate	2023
dc.date.none.fl_str_mv	2023 2023-12-26 2023 2023-12-26 2024 2024-05-07
dc.type.none.fl_str_mv	journal article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	http://hdl.handle.net/20.500.12105/19273
url	http://hdl.handle.net/20.500.12105/19273
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	Cell Press
publisher.none.fl_str_mv	Cell Press
dc.source.none.fl_str_mv	reponame:Repisalud instname:Instituto de Salud Carlos III (ISCIII)
instname_str	Instituto de Salud Carlos III (ISCIII)
reponame_str	Repisalud
collection	Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15.812429

IL-18-induced HIF-1α in ILC3s ameliorates the inflammation of C. rodentium-induced colitis.

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