iScience (Feb 2025)
IL-23 tunes inflammatory functions of human mucosal-associated invariant T cells
- 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
Affiliations
- Laetitia Camard
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, France
- Tharshana Stephen
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, France; scBiomarkers, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, France
- Hanane Yahia-Cherbal
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, France
- Vincent Guillemot
- Bioinformatics and Biostatistics Hub, Institut Pasteur, Université Paris Cité, 75015 Paris, France
- Sébastien Mella
- scBiomarkers, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, France; Bioinformatics and Biostatistics Hub, Institut Pasteur, Université Paris Cité, 75015 Paris, France
- Victoire Baillet
- Bioinformatics and Biostatistics Hub, Institut Pasteur, Université Paris Cité, 75015 Paris, France
- Hélène Lopez-Maestre
- Bioinformatics and Biostatistics Hub, Institut Pasteur, Université Paris Cité, 75015 Paris, France
- Daniele Capocefalo
- Institut Pasteur, Université Paris Cité, CNRS UMR 3738, Machine Learning for Integrative Genomics Group, 75015 Paris, France
- Laura Cantini
- Institut Pasteur, Université Paris Cité, CNRS UMR 3738, Machine Learning for Integrative Genomics Group, 75015 Paris, France
- Claire Leloup
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, France
- Julie Marsande
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, France
- Katherine Garro
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, France
- Juan Sienes Bailo
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, France
- Ambre Dangien
- Immunoregulation 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, France
- Natalia Pietrosemoli
- Bioinformatics and Biostatistics Hub, Institut Pasteur, Université Paris Cité, 75015 Paris, France
- Milena Hasan
- scBiomarkers, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, France
- Huimeng Wang
- Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
- Sidonia B.G. Eckle
- Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
- Anne M. Fourie
- Janssen Research & Development, LLC, San Diego, CA 92121, USA
- Carrie Greving
- Janssen Research & Development, LLC, San Diego, CA 92121, USA
- Barbara Joyce-Shaikh
- Janssen Research & Development, LLC, San Diego, CA 92121, USA
- Raphaelle Parker
- Janssen Research & Development, Janssen-Cilag, 92130 Issy les Moulineaux, France
- Daniel J. Cua
- Janssen Research & Development, LLC, Spring House, PA 19002, USA
- Elisabetta Bianchi
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, France
- Lars Rogge
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Université Paris Cité, 75015 Paris, France; Corresponding author
- DOI
- https://doi.org/10.1016/j.isci.2025.111898
- Journal volume & issue
-
Vol. 28,
no. 2
p. 111898
Abstract
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.
Keywords
