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

Authors:

• Camard, Laetitia
• Stephen, Tharshana
• Yahia-Cherbal, Hanane
• Guillemot, Vincent
• Mella, Sébastien
• Baillet, Victoire
• Lopez-Maestre, Hélène
• Capocefalo, Daniele
• Cantini, Laura
• Leloup, Claire
• Marsande, Julie
• Garro, Katherine
• Sienes Bailo, Juan
• Dangien, Ambre
• Pietrosemoli, Natalia
• Hasan, Milena
• Wang, Huimeng
• Eckle, Sidonia B.G.
• Fourie, Anne M.
• Greving, Carrie
• Joyce-Shaikh, Barbara
• Parker, Raphaelle
• Cua, Daniel J.
• Bianchi, Elisabetta
• Rogge, Lars

Details:

iScience, Volume 28, Issue 2, 2025-02-21

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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.