MAIT cells protect against sterile lung injury

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. MAIT cells were isolated from lung of C57BL/6 mouse challenged by bleomycin without previous intranasal BRD509 infection. Mouse Lung was collected before bleomycin challenge and 3 days and 7 days post bleomycin challenge. 27 mice were used, lung of 9 mice were collected before challenge, day 3 or day 7 post challenge, respectively. Resuspended lung cells from 3 mice were pool together to sort MAIT cells so that each time point has 3 samples of sorted MAIT cells for sequencing.