Expression and correlation analysis of VISTA in peripheral blood mononuclear cells of myasthenia gravis patients.

Myasthenia gravis (MG) is a T cell-dependent, B cell-mediated disorder strongly associated with antigen presentation by dendritic cells (DCs). In MG, mucosal tolerance is linked to increased expression of TGF-β mRNA in monocytes. Additionally, monocytic myeloid-derived suppressor cells (M-MDSCs) exhibit negative immunomodulatory effects by suppressing autoreactive T and B cells. In short, all these cells play an important role in the occurrence of MG. V domain-containing Ig suppressor of T-cell activation (VISTA) is an immune checkpoint molecule constitutively expressed on dendritic cells (DCs), CD4, CD8 T cells, monocytes and M-MDSCs. Similar to CTLA-4 and PD-1, VISTA controls peripheral tolerance and autoimmune disorder. VISTA expressed on APCs acts as a ligand to suppress the proliferation and cytokine production of both CD4 and CD8 T cells. VISTA expressed on CD4 T cells also suppresses T cell activation in a T-cell autonomous manner. Thus, VISTA may also play an important role in the immune regulation of MG disease. To investigate the role of VISTA in MG pathogenesis, we collected peripheral blood mononuclear cells (PBMCs) from MG patients and detected VISTA expression in different immune cell populations by FACs. VISTA expression was increased in CD4 T cells, CD8 T cells, B cells, monocytes, DCs, and M-MDSCs of PBMCs from MG patients. Correlation analysis further demonstrated that VISTA expression in monocytes was correlated with anti-AChR-IgG levels and MG-ADL scores. VISTA expression was positively associated with IL-4, TGF-β, Foxp3, IL-10, and TNF-α mRNA and negatively associated with IL-1β and IL-6 mRNA in MG PBMCs. VISTA can inhibit expression of IL-6 and TNF-α in vitro. These results suggest that VISTA may modulate MG disease progression and indicate the potential utility of VISTA agonists in MG treatment.