Mucosal-associated invariant T cells promote inflammation and exacerbate disease in murine models of arthritis

Abstract

Objective: The function of mucosal-associated invariant T (MAIT) cells remains largely unknown. We previously reported an immunoregulatory role of MAIT cells in an animal model of multiple sclerosis. The aim of this study was to use animal models to determine whether MAIT cells are involved in the pathogenesis of arthritis.

Methods: MR1-/- and MR1+/+ DBA/1J mice were immunized with bovine type II collagen (CII) in complete Freund's adjuvant to trigger collagen-induced arthritis (CIA). To assess CII-specific T cell recall responses, lymph node cells from mice with CIA were challenged with CII ex vivo, and cytokine production and proliferation were evaluated. Serum levels of CII-specific antibodies were measured by enzyme-linked immunosorbent assay. Collagen antibody-induced arthritis (CAIA) was induced in MR1-/- and MR1+/+ C57BL/6 mice by injection of anti-CII antibodies followed by injection of lipopolysaccharide. To demonstrate the involvement of MAIT cells in arthritis, we induced CAIA in MR1-/- C57BL/6 mice that had been reconstituted with adoptively transferred MAIT cells. MAIT cell activation in response to cytokine stimulation was investigated.

Results: The severity of CIA was reduced in MR1-/- DBA/1J mice. However, T and B cell responses to CII were comparable in MR1-/- and MR1+/+ DBA/1J mice. MR1-/- C57BL/6 mice were less susceptible to CAIA, and reconstitution with MAIT cells induced severe arthritis in MR1-/- C57BL/6 mice, demonstrating an effector role of MAIT cells in arthritis. MAIT cells became activated upon stimulation with interleukin-23 (IL-23) or IL-1β in the absence of T cell receptor stimuli.

Conclusion: These results indicate that MAIT cells exacerbate arthritis by enhancing the inflammation.