117 Mucosal-associated invariant t cell deficiency in systemic lupus erythematosus is related to to an intrinsic defect in the ca2+/calcineurin/nfat1 signallingpathway

Background and aims Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections and play an important role in mucosal immunity. Here, we examined the level and function of MAIT cells in patients with rheumatic diseases. Methods Patients with systemic lupus erythematosus (SLE; n=54), rheumatoid arthritis (RA; n=66), Behcet’s disease (n=9), ankylosing spondylitis (n=21), and healthy controls (n=136) were enrolled in the study. MAIT cell, cytokine and programmed death-1 (PD-1) levels were measured by flow cytometry. Results Circulating MAIT cell levels were significantly reduced in SLE and RA patients. This MAIT cell deficiency was more prominent in CD8+ and double-negative T cell subsets, and significantly correlated with disease activity, such as SLEDAI and DAS28. Interestingly, MAIT cell frequency was significantly correlated with natural killer T (NKT) cell frequency in SLE patients. IFN-γ in MAIT cells was impaired in SLE patients, which was due to an intrinsic defect in the Ca2+/calcineurin/NFAT1 signalling pathway. In SLE patients, MAIT cells were poorly activated by alpha-galactosylceramide-stimulated NKT cells, thereby showing the dysfunction between MAIT cells and NKT cells. Notably, an elevated expression of PD-1 in MAIT cells and NKT cells was associated with SLE. In RA patients, MAIT cell levels were significantly higher in synovial fluid than in peripheral blood. Conclusions Our study primarily demonstrates that MAIT cells are numerically and functionally deficient in SLE. In addition, we report a novel finding that this MAIT cell deficiency is associated with NKT cell deficiency and elevated PD-1 expression.