Background/Purpose: Mucosal-associated invariant T (MAIT) cells are subsets of innate invariant T cells and rapidly produce Th1/Th17 cytokines including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-17 in an innate-like manner. Accumulating data indicate that MAIT cells play an important role in immune defense against infection or cancer. Furthermore, recent studies have extended knowledge regarding the clinical relevance of MAIT cells to cardiometabolic diseases, including metabolic syndrome, obesity, diabetes mellitus, and cardiovascular disease. Here, we investigate the role of MAIT cells in gouty arthritis (GA), one of metabolic diseases, and their effects on osteoclastogenesis.

Methods: Patients with GA (n = 61), hyperuricemia subjects (n = 11), and healthy controls (n = 30) were enrolled in this study. MAIT cells, cytokines, CD69, programmed death-1 (PD-1), and lymphocyte-activation gene 3 (LAG-3) levels were measured by flow cytometry. In vitro osteoclastogenesis experiments were performed using peripheral blood mononuclear cells in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor kB ligand.

Results: Circulating MAIT cell levels were significantly reduced in GA patients. However, their capacities for IFN-γ, IL-17, and TNF-α production were preserved. Expression levels of CD69, PD-1, and LAG-3 in MAIT cells were found to be elevated in GA patients. In particular, CD69 expression in circulating MAIT cells was increased by stimulation with monosodium urate monohydrate (MSU) crystals, suggesting that deposition of MSU crystal might contribute to MAIT cell activation. Interestingly, MAIT cells were found to be accumulated in synovial fluid and infiltrated into gouty tophus tissues within joints. Furthermore, activated MAIT cells secreted pro-resorptive cytokines (i.e., IL-6, IL-17, and TNF-α) and facilitated osteoclastogenesis.

Conclusion: This study demonstrates that circulating MAIT cells are activated and numerically deficient in GA patients. In addition, MAIT cells have the potential to migrate to inflamed tissues and induce osteoclastogenesis. These findings provide an important role of MAIT cells in the pathogenesis of inflammation and bone destruction in GA patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/altered-distribution-and-enhanced-osteoclastogenesis-of-mucosal-associated-invariant-t-cells-in-gouty-arthritis/