Analysis of Gut-Homing Receptors in Circulating Mucosal-Associated Invariant T Cells and Their Presence in Synovial Tissue From Patients With Axial Spondyloarthritis

Abstract

Objective: Mucosal-Associated invariant T (MAIT) cells have been identified as being involved in the pathophysiology of axial spondyloarthritis (axSpA). We aimed to further investigate the phenotype of circulating MAIT cells in patients with axSpA by assessing the expression of an activation marker and Gut-Homing receptors, as well as the effects of tumor necrosis factor (TNF) blockade. The presence of MAIT cells in synovial biopsies from patients with axSpA was also studied.

Methods: Blood samples were obtained from 26 patients with axSpA (11 radiographic, 15 nonradiographic) and 27 healthy controls (HCs). Frequency of Vα7.2+CD161+ MAIT cells was determined in both the axSpA and HC groups. Expression of CD69, CCR9, and CD49d on MAIT cells was analyzed by flow cytometry. The presence of MAIT cells was examined in synovial biopsy samples from 3 patients with axSpA and compared to synovial biopsies from 3 patients with rheumatoid arthritis and 4 with osteoarthritis by confocal microscopy.

Results: Patients with axSpA were characterized by a higher frequency of CD3+ and CD8+ MAIT cells expressing CD69, CCR9, and CD49d, especially in the radiographic subgroup. MAIT cells were detected in a synovial biopsy sample from 1 patient with axSpA. After TNF blockade, a decrease in the frequency of MAIT cells and TNF/interleukin 17A-producing MAIT cells was observed.

Conclusion: MAIT cells were activated and expressed Gut-Homing receptors, indicating their potential involvement in the gut-joint axis in axSpA. MAIT cell frequency and function were reduced by TNF blockade. MAIT cells could be found in synovial tissue in patients with axSpA.

Keywords: MAIT cells; axial spondyloarthritis; gut; innate-like T cells; synovium.