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

Archive ouverte

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

Edité par CCSD -

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.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion