IL-23 tunes inflammatory functions of human mucosal-associated invariant T cells
Summary: IL-23 signaling plays a key role in the pathogenesis of chronic inflammatory and infectious diseases, yet the cellular targets and signaling pathways affected by this cytokine remain poorly understood. We show that IL-23 receptors are expressed on the large majority of human mucosal-associa...
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| Language: | English |
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Elsevier
2025-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225001580 |
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| author | Laetitia Camard Tharshana Stephen Hanane Yahia-Cherbal Vincent Guillemot Sébastien Mella Victoire Baillet Hélène Lopez-Maestre Daniele Capocefalo Laura Cantini Claire Leloup Julie Marsande Katherine Garro Juan Sienes Bailo Ambre Dangien Natalia Pietrosemoli Milena Hasan Huimeng Wang Sidonia B.G. Eckle Anne M. Fourie Carrie Greving Barbara Joyce-Shaikh Raphaelle Parker Daniel J. Cua Elisabetta Bianchi Lars Rogge |
| author_facet | Laetitia Camard Tharshana Stephen Hanane Yahia-Cherbal Vincent Guillemot Sébastien Mella Victoire Baillet Hélène Lopez-Maestre Daniele Capocefalo Laura Cantini Claire Leloup Julie Marsande Katherine Garro Juan Sienes Bailo Ambre Dangien Natalia Pietrosemoli Milena Hasan Huimeng Wang Sidonia B.G. Eckle Anne M. Fourie Carrie Greving Barbara Joyce-Shaikh Raphaelle Parker Daniel J. Cua Elisabetta Bianchi Lars Rogge |
| author_sort | Laetitia Camard |
| collection | DOAJ |
| description | Summary: IL-23 signaling plays a key role in the pathogenesis of chronic inflammatory and infectious diseases, yet the cellular targets and signaling pathways affected by this cytokine remain poorly understood. We show that IL-23 receptors are expressed on the large majority of human mucosal-associated invariant T (MAIT), but not of conventional T cells. Protein and transcriptional profiling at the population and single cell level demonstrates that stimulation with IL-23 or the structurally related cytokine IL-12 drives distinct functional profiles, revealing a high level of plasticity of MAIT cells. IL-23, in particular, affects key molecules and pathways related to autoimmunity and cytotoxic functions. Integrated analysis of transcriptomes and chromatin accessibility, supported by CRISPR-Cas9 mediated deletion, shows that AP-1 transcription factors constitute a key regulatory node of the IL-23 pathway in MAIT cells. In conclusion, our findings indicate that MAIT cells are key mediators of IL-23 functions in immunity to infections and chronic inflammatory diseases. |
| format | Article |
| id | doaj-art-98a96ee5396d458b9e7ae68f7e9ba99a |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-98a96ee5396d458b9e7ae68f7e9ba99a2025-02-09T05:00:59ZengElsevieriScience2589-00422025-02-01282111898IL-23 tunes inflammatory functions of human mucosal-associated invariant T cellsLaetitia Camard0Tharshana Stephen1Hanane Yahia-Cherbal2Vincent Guillemot3Sébastien Mella4Victoire Baillet5Hélène Lopez-Maestre6Daniele Capocefalo7Laura Cantini8Claire Leloup9Julie Marsande10Katherine Garro11Juan Sienes Bailo12Ambre Dangien13Natalia Pietrosemoli14Milena Hasan15Huimeng Wang16Sidonia B.G. Eckle17Anne M. Fourie18Carrie Greving19Barbara Joyce-Shaikh20Raphaelle Parker21Daniel J. Cua22Elisabetta Bianchi23Lars Rogge24Immunoregulation Unit, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, FranceImmunoregulation Unit, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, France; scBiomarkers, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, FranceImmunoregulation Unit, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, FranceBioinformatics and Biostatistics Hub, Institut Pasteur, Université Paris Cité, 75015 Paris, FrancescBiomarkers, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, France; Bioinformatics and Biostatistics Hub, Institut Pasteur, Université Paris Cité, 75015 Paris, FranceBioinformatics and Biostatistics Hub, Institut Pasteur, Université Paris Cité, 75015 Paris, FranceBioinformatics and Biostatistics Hub, Institut Pasteur, Université Paris Cité, 75015 Paris, FranceInstitut Pasteur, Université Paris Cité, CNRS UMR 3738, Machine Learning for Integrative Genomics Group, 75015 Paris, FranceInstitut Pasteur, Université Paris Cité, CNRS UMR 3738, Machine Learning for Integrative Genomics Group, 75015 Paris, FranceImmunoregulation Unit, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, FranceImmunoregulation Unit, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, FranceImmunoregulation Unit, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, FranceImmunoregulation Unit, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, FranceImmunoregulation Unit, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, France; Department of Dermatology, Hôpital Cochin, AP-HP, AP-HP Centre-Université de Paris, 75014 Paris, FranceBioinformatics and Biostatistics Hub, Institut Pasteur, Université Paris Cité, 75015 Paris, FrancescBiomarkers, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, FranceDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, AustraliaDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, AustraliaJanssen Research & Development, LLC, San Diego, CA 92121, USAJanssen Research & Development, LLC, San Diego, CA 92121, USAJanssen Research & Development, LLC, San Diego, CA 92121, USAJanssen Research & Development, Janssen-Cilag, 92130 Issy les Moulineaux, FranceJanssen Research & Development, LLC, Spring House, PA 19002, USAImmunoregulation Unit, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, FranceImmunoregulation Unit, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, France; Corresponding authorSummary: IL-23 signaling plays a key role in the pathogenesis of chronic inflammatory and infectious diseases, yet the cellular targets and signaling pathways affected by this cytokine remain poorly understood. We show that IL-23 receptors are expressed on the large majority of human mucosal-associated invariant T (MAIT), but not of conventional T cells. Protein and transcriptional profiling at the population and single cell level demonstrates that stimulation with IL-23 or the structurally related cytokine IL-12 drives distinct functional profiles, revealing a high level of plasticity of MAIT cells. IL-23, in particular, affects key molecules and pathways related to autoimmunity and cytotoxic functions. Integrated analysis of transcriptomes and chromatin accessibility, supported by CRISPR-Cas9 mediated deletion, shows that AP-1 transcription factors constitute a key regulatory node of the IL-23 pathway in MAIT cells. In conclusion, our findings indicate that MAIT cells are key mediators of IL-23 functions in immunity to infections and chronic inflammatory diseases.http://www.sciencedirect.com/science/article/pii/S2589004225001580ImmunologyTranscriptomics |
| spellingShingle | Laetitia Camard Tharshana Stephen Hanane Yahia-Cherbal Vincent Guillemot Sébastien Mella Victoire Baillet Hélène Lopez-Maestre Daniele Capocefalo Laura Cantini Claire Leloup Julie Marsande Katherine Garro Juan Sienes Bailo Ambre Dangien Natalia Pietrosemoli Milena Hasan Huimeng Wang Sidonia B.G. Eckle Anne M. Fourie Carrie Greving Barbara Joyce-Shaikh Raphaelle Parker Daniel J. Cua Elisabetta Bianchi Lars Rogge IL-23 tunes inflammatory functions of human mucosal-associated invariant T cells iScience Immunology Transcriptomics |
| title | IL-23 tunes inflammatory functions of human mucosal-associated invariant T cells |
| title_full | IL-23 tunes inflammatory functions of human mucosal-associated invariant T cells |
| title_fullStr | IL-23 tunes inflammatory functions of human mucosal-associated invariant T cells |
| title_full_unstemmed | IL-23 tunes inflammatory functions of human mucosal-associated invariant T cells |
| title_short | IL-23 tunes inflammatory functions of human mucosal-associated invariant T cells |
| title_sort | il 23 tunes inflammatory functions of human mucosal associated invariant t cells |
| topic | Immunology Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225001580 |
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