biostudies-literatureUnknown28(2)Camard LFoundation for Medical ResearchJ&J Innovative MedicineInstitut PasteurIL-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 mediScience111898https://www.ebi.ac.uk/biostudies/studies/S-EPMC11850163biostudies-literatureIL-23 tunes inflammatory functions of human mucosal-associated invariant T cells.PMC11850163Yahia-Cherbal HCua DJCamard LWang HStephen TPietrosemoli NLeloup CCantini LHasan MBaillet VParker RBianchi EMella SGuillemot VGreving CJoyce-Shaikh BLopez-Maestre HRogge LCapocefalo DEckle SBGMarsande JDangien AFourie AMGarro KSienes Bailo JfalseIL-23 tunes inflammatory functions of human mucosal-associated invariant T cells.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 med2025-01-01T00:00:00Z2025 Feb2026-06-01T21:16:04.342Z2025-04-06T10:34:18.397ZS-EPMC118501634000835910.1016/j.isci.2025.111898