IL-23 tunes inflammatory functions of human mucosal-associated invariant T cells

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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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:iScience
Subjects:
Immunology
Transcriptomics
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225001580
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Summary: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.
ISSN:2589-0042

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