MAIT cells protect against sterile lung injury (scRNA-Seq)

Mucosal-associated invariant T (MAIT) cells, the most abundant unconventional T cells in the lung, have been recently linked to tissue protection and repair. 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 induces an accompanying tissue repair programme, associated with a protective role against bleomycin-induced lung injury. MAIT cells drive the accumulation of type 1 conventional dendritic cells (cDC1), 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 defence against sterile lung injury by fostering cDC1-driven anti-fibrotic pathways. Lung was collected from C57BL/6 and Mr1 mouse day 0 (with PBS challenge), day 3, day 7 post bleomycin challenge. Each genotype and time point had 3 replicates. Live cells were sorted. Cells from 2 mice were mixed together for single cell sequencing after staining with TotalSeq-C Mouse Universal Cocktail (BioLegend, Cat. No. 199903) and TotalSeq-C HashTag Antibody (BioLegend, Cat. No. 155861, 155863).