Fibrinogen-like protein-2 causes deterioration in cardiac function in experimental autoimmune myocarditis rats through regulation of programmed death-1 and inflammatory cytokines.

Programmed death-1 (PD-1) plays an important role in protecting against inflammation and myocyte damage in T-cell-mediated myocarditis. To understand whether fibrinogen-like protein-2 (FGL2) can affect the role of the PD-1/PD-L1 pathway in experimental autoimmune myocarditis (EAM), we investigated cardiac function in EAM rats over-expressing FGL2. Over-expression of FGL2 significantly decreased PD-1 and deteriorated cardiac function in rats with autoimmune myocarditis. Histopathology revealed increased inflammatory cell infiltrate in EAM-FGL2 rats compared with the control groups (EAM, EAM-GFP and NC). Notably, transcription factor forkhead box P3 (Foxp3) and retinoic acid-related orphan receptor γt (RORγt) protein and mRNA levels were statistically (P < 0·05) increased in EAM rats. We also found that interferon-γ, interleukin-6, interleukin-17 and brain natriuretic peptide levels were profoundly increased in serum of FGL2 over-expressing EAM rats. Hence, FGL2 plays an important role in the pathogenesis of autoimmune myocarditis that also involves the PD-1/PD-L1 pathway. Our findings may provide novel therapeutic targets for the treatment of immune-induced heart injury.