AB0139 Role of mucosal-associated invariant t (MAIT) cells in a lupus model
Authors: G Murayama, A Chiba, A Nomura, H Amano, K Yamaji, N Tamura, S Miyake
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Mucosal-associated invariant T (MAIT) cells are innate T cells that are restricted by MHC-related molecule-1 (MR1) and express a semi-invariant TCRα chain: Vα7.2-Jα33 in humans and Vα19-Jα33 in mice. Previously, we have demonstrated that MAIT cells played a protective role against experimental autoimmune encephalomyelitis, an animal model of human multiple sclerosis. We found that MAIT cells are activated in patients with systemic lupus erythematosus (SLE) and that the activation state of MAIT cells correlated with SLE disease activity index (SLEDAI) score, suggesting their association in lupus pathology. <h3>Objectives</h3> We set out to clarify functions of MAIT cells in a lupus model by using FcγRIIB<sup>-/-</sup> Yaa mice. <h3>Methods</h3> FcγRIIB<sup>-/-</sup> Yaa mice were crossed to MR1 deficient mice lacking MAIT cells, and disease progression was compared between MR1<sup>-/-</sup> FcγRIIB<sup>-/-</sup> Yaa and MR1<sup>+/+</sup>FcγRIIB<sup>-/-</sup> Yaa mice at 1–4 months of age. Serum anti-dsDNA antibody levels were measured and urinary microalbumin were evaluated. At the time of sacrifice, at 4 months of age, the severity of nephritis and dermatitis were assessed by histologically and IgG deposition in skin and glomeruli was measured. <h3>Results</h3> Survival rate was significantly reduced in MR1<sup>-/-</sup> FcγRIIb<sup>-/-</sup> Yaa mice compared with MR1<sup>+/+</sup> FcγRIIb<sup>-/-</sup> Yaa mice. Anti-dsDNA antibody levels were remarkably higher in MR1<sup>+/+</sup> than MR1<sup>-/-</sup> FcγRIIb<sup>-/-</sup> Yaa mice at 4 months of age. Even though Glomeruli were significantly enlarged both in MR1<sup>+/+</sup> and MR1<sup>-/-</sup> FcγRIIb<sup>-/-</sup> Yaa mice due to a marked cellular proliferation in glomeruli, the glomerulonephritis score tended to be lower in MR1<sup>-/-</sup> FcγRIIb<sup>-/-</sup> Yaa mice compared with MR1<sup>+/+</sup> FcγRIIb<sup>-/-</sup> Yaa mice. A larger amount of IgG deposition was observed in mesangial area and along glomerular capillary walls in MR1<sup>-/-</sup> than MR1<sup>+/+</sup> FcγRIIb<sup>-/-</sup> Yaa mice. However, MR1<sup>-/-</sup> FcγRIIB<sup>-/-</sup> Yaa mice showed exacerbated inflammation in the skin lesions. There was a high degree of inflammatory cells infiltration into the skin and a significant worsening of dermatitis score in MR1<sup>-/-</sup> FcγRIIb<sup>-/-</sup> Yaa mice compared to MR1<sup>+/+</sup>FcγRIIb<sup>-/-</sup> Yaa mice. <h3>Conclusions</h3> These data suggests that MAIT cells exhibit dual roles in lupus pathogenesis. MAIT cells enhance autoantibody production and the disease severity of nephritis, but have a suppressive effect on dermatitis. Further studies are under going to uncover the mechanisms by which MAIT cells are involved in each target tissues. <h3>References</h3> Croxford JL, et al. Invariant V(alpha)19i T cells regulate autoimmune inflammation. Nat Immunol. 2006; 7(9): 987–94. Chiba A, et al. Mucosal-associated invariant T cells promote inflammation and exacerbate disease in murine models of arthritis. Arthritis Rheum. 2012; 64(1): 153–61. Kawano S, et al. Phenotype conversion from rheumatoid arthritis to systemic lupus erythematosus by introduction of Yaa mutation into FcγRIIB-deficient C57BL/6 mice. Eur J Immunol. 2013; 43(3): 770–8. <h3>Disclosure of Interest</h3> None declared