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

Camard, L.; Stephen, T.; Yahia-Cherbal, H.; Guillemot, V.; Mella, S.; Baillet, V.; Lopez-Maestre, H.; Capocefalo, D.; Cantini, L.; Leloup, C.; Marsande, J.; Sienes Bailo, J.; Dangien, A.; Pietrosemoli, N.; Hasan, M.; Wang, H.; Eckle, S. B. G.; Fourie, A. M.; Greving, C.; Shaikh, B. J.; Parker, R.; Cua, D. J.; Bianchi, E.; Rogge, L.

doi:10.1101/2024.08.29.609178

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bioRxiv · 10.1101/2024.08.29.609178

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

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Abstract

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 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 transcriptomic 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.

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Camard, L., Stephen, T., Yahia-Cherbal, H., Guillemot, V., Mella, S., Baillet, V., Lopez-Maestre, H., Capocefalo, D., Cantini, L., Leloup, C., Marsande, J., Sienes Bailo, J., Dangien, A., Pietrosemoli, N., Hasan, M., Wang, H., Eckle, S. B. G., Fourie, A. M., Greving, C., Shaikh, B. J., Parker, R., Cua, D. J., Bianchi, E., Rogge, L.. 2024-08-30. IL-23 tunes inflammatory functions of human mucosal-associated invariant T (MAIT) cells. https://doi.org/10.1101/2024.08.29.609178

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