Role of mucosal-associated invariant T cells in lupus pathogenesis. — ASN Events
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  3. Role of mucosal-associated invariant T cells in lupus pathogenesis.

Role of mucosal-associated invariant T cells in lupus pathogenesis. (#114)

Goh Murayama 1 , Asako Chiba 1 , Ken Yamaji 1 , Naoto Tamura 1 , Sachiko Miyake 1
  1. JUNTENDO UNIVERSITY SCHOOL OF MEDICINE, TOKYO, JAPAN, Bunkyo-ku, TOKYO, Japan

Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies. Previously we reported association of MAIT cell activation with disease activity in patients with systemic lupus erythematosis. In this study, We set out to clarify functions of MAIT cells in a lupus model by using FcγRIIB-/- Yaa mice.

Methods: FcγRIIB-/-Yaa mice were crossed to MR1 deficient mice lacking MAIT cells, and disease progression was compared between MR1KO FcγRIIB-/- Yaa and MR1+/+ FcγRIIB-/- Yaa mice at 1-4 months of age. T follicular helper cells (TFH cells) and regulatory T cells (Tregs) among splenocytes from these mice were analyzed by using flowcytometer.

Results: MR1KO FcγRIIB-/-Yaa mice showed a reduction of serum anti-dsDNA antibody levels and an increase of survival rate. There was a trend of less proteinuria and less severe nephritis in MR1KO FcγRIIB-/-Yaa mice. MR1KO FcγRIIB-/-Yaa mice developed exacerbated inflammation in the skin lesions with a higher histopathological dermatitis score compared to MR1+/+ FcγRIIB-/-Yaa mice. Flow cytometric analysis of splenocytes revealed that the proportion of TFH cells was decreased but that of Tregs was increased in MR1KO FcγRIIb-/-Yaa mice compared to MR1+/+ FcγRIIb-/-Yaa mice.

Conclusions: 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.