IL-18-induced HIF-1α in ILC3s ameliorates the inflammation of C. rodentium-induced colitis
Summary: 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 infecti...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-12-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723015206 |
| _version_ | 1797448049933418496 |
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| author | Ana Valle-Noguera Lucía Sancho-Temiño Raquel Castillo-González Cristina Villa-Gómez María José Gomez-Sánchez Anne Ochoa-Ramos Patricia Yagüe-Fernández Blanca Soler Palacios Virginia Zorita Berta Raposo-Ponce José María González-Granado Julián Aragonés Aránzazu Cruz-Adalia |
| author_facet | Ana Valle-Noguera Lucía Sancho-Temiño Raquel Castillo-González Cristina Villa-Gómez María José Gomez-Sánchez Anne Ochoa-Ramos Patricia Yagüe-Fernández Blanca Soler Palacios Virginia Zorita Berta Raposo-Ponce José María González-Granado Julián Aragonés Aránzazu Cruz-Adalia |
| author_sort | Ana Valle-Noguera |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-09T14:04:46Z |
| format | Article |
| id | doaj.art-5b260e4b11834ac38bde4e1b0ddc5764 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-09T14:04:46Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-5b260e4b11834ac38bde4e1b0ddc57642023-11-30T05:07:20ZengElsevierCell Reports2211-12472023-12-014212113508IL-18-induced HIF-1α in ILC3s ameliorates the inflammation of C. rodentium-induced colitisAna Valle-Noguera0Lucía Sancho-Temiño1Raquel Castillo-González2Cristina Villa-Gómez3María José Gomez-Sánchez4Anne Ochoa-Ramos5Patricia Yagüe-Fernández6Blanca Soler Palacios7Virginia Zorita8Berta Raposo-Ponce9José María González-Granado10Julián Aragonés11Aránzazu Cruz-Adalia12Department of Immunology, Ophthalmology and ENT, School of Medicine, Complutense University of Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, SpainDepartment of Immunology, Ophthalmology and ENT, School of Medicine, Complutense University of Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, SpainDepartment of Immunology, Ophthalmology and ENT, School of Medicine, Complutense University of Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, SpainDepartment of Immunology, Ophthalmology and ENT, School of Medicine, Complutense University of Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, SpainDepartment of Immunology, Ophthalmology and ENT, School of Medicine, Complutense University of Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, SpainDepartment of Immunology, Ophthalmology and ENT, School of Medicine, Complutense University of Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, SpainCentro de Investigaciones Biológicas Margarita Salas (CIB-CSIC), Madrid, SpainDepartment of Immunology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, SpainCentro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, SpainCentro de Biología Molecular Severo Ochoa (CBM-CSIC), Madrid, SpainDepartment of Immunology, Ophthalmology and ENT, School of Medicine, Complutense University of Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain; CIBER de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, SpainHospital Santa Cristina, Fundación de Investigación Hospital de la Princesa, Madrid, Spain; CIBER de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, SpainDepartment of Immunology, Ophthalmology and ENT, School of Medicine, Complutense University of Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723015206CP: Immunology |
| spellingShingle | Ana Valle-Noguera Lucía Sancho-Temiño Raquel Castillo-González Cristina Villa-Gómez María José Gomez-Sánchez Anne Ochoa-Ramos Patricia Yagüe-Fernández Blanca Soler Palacios Virginia Zorita Berta Raposo-Ponce José María González-Granado Julián Aragonés Aránzazu Cruz-Adalia IL-18-induced HIF-1α in ILC3s ameliorates the inflammation of C. rodentium-induced colitis Cell Reports CP: Immunology |
| title | 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_short | 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 |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723015206 |
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