Mucosal associated invariant T (MAIT) cells are innate like lymphocytes found in peripheral blood and mucosa; they are decreased during systemic lupus erythematosus and other auto-immune diseases. However, MAIT cell levels and functions have not previously been investigated in dermatomyositis (DM). Herein, we studied MAIT cells level and activation status before and after treatment during DM (n=21) and compared them to healthy controls (n=19), psoriasis (n=7) and atopic dermatitis (n=5).
We showed that DM was associated with a dramatic reduced number of circulating MAIT cells (median: 0.12% [0.073-0.25%] versus 2.13% [1.05-3.94%], p < 0.0001). This disappearance was specific to DM. Residual MAIT cells displayed an activated/exhausted phenotype with higher expression of CD25, CD39, CTLA4 and increase of the TEMRA state. We found an inverse correlation between CD25 and CTLA4 expression on MAIT cells and the level of circulating MAIT cells. After a median follow up of 0.9 year, we observed a slight increase of MAIT cells (median: 0.25% [0.24-0.60%] versus 0.73% [0.47-1.16%], p = 0.002). Nevertheless, it did not return to normal healthy controls level. We next compared skin from DM with healthy controls for PLZF, the master transcript of MAIT cells thanks to microarray analysis. PLZF was not elevated in lesional skin. Finally, preliminary in vitro assays showed that strong stimulation by both TCR and IL-12 and IL-18, cytokines elevated during DM and known to activate MAIT cells, leaded to decreased expression of CD161 and higher mortality.
Taken together, our data indicate that in DM peripheral blood MAIT cells, which are thought to have regulatory role, are dramatically reduced in relationship with an activated abnormal phenotype potentially leading to activation induced cell death rather than their migration in affected tissue.

Persistent deficiency of mucosal associated invariant T cells in dermatomyositis