PWE-088 Frequency and function of anti-bacterial mait cells are significantly impaired in advanced alcoholic liver disease

Introduction Intestinal bacterial translocation and systemic gut-derived bacterial products play a central role in the immunopathogenesis of alcoholic liver disease (ALD), yet the mechanisms of susceptibility to infection and the link with intestinal immunity remain elusive. Mucosal associated invariant T cells (MAIT) are unconventional T cells which only respond to bacteria-derived metabolites and are found in large numbers in the blood, intestinal mucosae and liver. They represent a key sentinel system for the homeostatic control of the gut flora and for the control of bacterial infections. The aim of this study was to assess the role of MAIT cells in ALD. Method Peripheral blood mononuclear cells from subjects with acute alcoholic hepatitis (AAH, Maddrey’s discriminant function >32; n = 9), compensated alcohol-related cirrhosis (ARC, n = 9) and healthy controls (HC, n = 9) were examined by FACS. MAIT cells were identified as CD161 + /Vα7.2+ CD8 + T cells and MAIT-presenting cells (MPC) as MR1+ monocytes or B cells. We quantified (1) frequency, activation status (CD69/HLA-DR) and immunoinhibitory signatures (PD1/TIM3/LAG3) of MAIT cells; (2) frequency and immunoinhibitory status (PD1/PDL1/TIM3/mGal9) of MPC; (3) cytokine/cytotoxicity profiles (IFNγ/TNFα/IL17; GranzymeB (GrB)/Perforin/CD107a) of MAIT cells after in-vitro stimulation with fixed E. Coli. Plasma cytokines and endotoxin levels were assessed by ELISA. Results MAIT frequencies were reduced in ARC (p = 0.005) and dramatically lower in AAH (p Conclusion This is the first report addressing the role of MAIT cells in liver disease. We show that MAIT cells have quantitative and functional impairments in ALD, with defective TNFα and IL17 responses, increased killing potential and overexpression of immunoinhibitory receptors. MAIT cells may represent a novel immunotherapeutic target for ALD. Disclosure of interest None Declared.