MAIT cells protect against sterile lung injury (BRD509)

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. For RNA-seq of MAIT cells, MAIT cells were isolated from lung of C57BL/6 mouse challenged by bleomycin or PR8 IAV with previous intranasal Salmonella Typhimurium BRD509 infection. For MAIT cells isolated after bleomycin challenge, mouse lung was collected on day 0 (with PBS challenge), day 3, day 7, day 14, day 21 and day 28 post bleomycin challenge. For MAIT cells isolated after PR8 IAV challenge, mouse lung was collected on day 0 (with PBS challenge), day 3, day 5, day 7 and day 13 post PR8 challenge. For total lung RNA-seq, total lung was collected from C57BL/6 and Mr1 mouse challenged by bleomycin day 0 (with PBS challenge), day 3, day 7, day 14 and day 21 post bleomycin challenge.