Role of MAIT cells in the pathophysiology of pulmonary fibrosis. – FIBROMAIT

Fibrotic interstitial lung diseases are a diverse group of chronic and progressive respiratory disorders, with idiopathic pulmonary fibrosis being the most common member. Evidence gleaned from animal modeling and human studies suggests that innate and adaptive immune processes can orchestrate existing fibrotic responses through a crosstalk with invading or commensal microbes in the lungs. Mucosal-Associated Invariant T cells (MAIT) are innate-like T cells recognizing bacteria-derived riboflavin precursor derivatives. In humans, MAIT cells represent a large proportion of T cells in the blood and barrier tissues, where they are anatomically close to epithelial surfaces. MAIT cells play an important role in antimicrobial immunity at mucosal sites, in particular the lung. Recent findings suggest broader functions of MAIT cells in immunity, including regulation of epithelial barrier integrity. Both human and mouse MAIT cells express a transcriptomic tissue repair signature upon stimulation. Inappropriate tissue repair ability of MAIT cells might participate in the development of pulmonary fibrosis, as observed in the liver. Based on our preliminary results, we hypothesize that MAIT cells could influence the development of pulmonary fibrosis. The main objectives of this project are 1) To characterize the role of MAIT cells in the genesis and progression of pulmonary fibrosis, 2) To study the crosstalk between MAIT cells and the lung microbiota to determine the temporal relationship between lung dysbiosis, inflammation, MAIT cell activation and fibrogenesis, and 3) To evaluate MAIT cell as a potential therapeutic target by using synthetic blocking or activating ligands. For that purpose, we will use both experimental mouse models and in vitro research on human tissues. As a perspective of interest, this may raise the possibility to use peripheral and lung MAIT cell phenotype as a novel biomarker for monitoring pulmonary fibrosis progression.