biostudies-literatureZhang XChina Scholarship CouncilUK Research and Innovation Medical Research CouncilWellcome Trust115275https://www.ebi.ac.uk/biostudies/studies/S-EPMC7617896biostudies-literatureUnknown44(2)Mucosal-associated invariant T (MAIT) cells, the most abundant unconventional T cells in the lung, can exhibit a wide range of functional responses to different triggers via their T cell receptor (TCR) and/or cytokines. Their role, especially in sterile lung injury, is unknown. Using single-cell RNA sequencing (scRNA-seq), spectral analysis, and adoptive transfer in a bleomycin-induced sterile lung injury, we found that bleomycin activates murine pulmonary MAIT cells and is associated with a protective role against bleomycin-induced lung injury. MAIT cells drive the accumulation of type 1 conventional dendritic cells (cDC1s), limiting tissue damage in a DNGR-1-dependent manner. Human scRNA-seq data revealed that MAIT cells were activated, with increased cDC populations in idiopathic pulmonary fibrosis patients. Thus, MAIT cells enhance defense against sterile lung injury by fostering cDC1-driven anti-fibrotic pathways.Cell reportsMAIT cells protect against sterile lung injury.PMC7617896104553/z/14/z211050/Z/18/z211050MR/R015708/1222426/Z/21/Z222426Greco MLi SZhang XHinks TSCKlenerman PLason WfalseMAIT cells protect against sterile lung injury.Mucosal-associated invariant T (MAIT) cells, the most abundant unconventional T cells in the lung, can exhibit a wide range of functional responses to different triggers via their T cell receptor (TCR) and/or cytokines. Their role, especially in sterile lung injury, is unknown. Using single-cell RNA sequencing (scRNA-seq), spectral analysis, and adoptive transfer in a bleomycin-induced sterile lung injury, we found that bleomycin activates murine pulmonary MAIT cells and is associated with a protective role against bleomycin-induced lung injury. MAIT cells drive the accumulation of type 1 conventional dendritic cells (cDC1s), limiting tissue damage in a DNGR-1-dependent manner. Human scRNA-seq data revealed that MAIT cells were activated, with increased cDC populations in idiopathic pulmonary fibrosis patients. Thus, MAIT cells enhance defense against sterile lung injury by fostering cDC1-driven anti-fibrotic pathways.2025-01-01T00:00:00Z2025 Feb2026-03-27T16:17:42.186Z2025-08-30T03:05:38.821ZS-EPMC76178963991895910.1016/j.celrep.2025.115275