Altered distribution and enhanced osteoclastogenesis of mucosal-associated invariant T cells in gouty arthritis

Author:

Cho Young-Nan1,Jeong Hae-Seong1,Park Ki-Jeong1,Kim Hyung-Seok2,Kim Eun-Hee2,Jin Hye-Mi1,Jung Hyun-Ju1,Ju Jae Kyun3,Choi Sung-Eun1,Kang Ji-Hyoun1,Park Dong-Jin1,Kim Tae-Jong1,Lee Shin-Seok1ORCID,Kee Seung-Jung4,Park Yong-Wook1

Affiliation:

1. Department of RheumatologyChonnam National University Medical School and Hospital, Gwangju, Republic of Korea

2. Department of Forensic MedicineChonnam National University Medical School and Hospital, Gwangju, Republic of Korea

3. Department of Surgery, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea

4. Department of Laboratory Medicine, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea

Abstract

Abstract Objective This study was designed to investigate the role of mucosal-associated invariant T (MAIT) cells in gouty arthritis (GA) and their effects on osteoclastogenesis. Methods Patients with GA (n = 61), subjects with hyperuricaemia (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 M-CSF and RANK 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 MSU crystals, suggesting that deposition of MSU crystals 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.

Funder

National Research Foundation of Korea

Korean Government

Chonnam National University Hospital Biomedical Research Institute

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

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