Paeoniflorin improves autoimmune myocarditis in young rat by inhibiting CXCR5 to reduce follicular helper T cells

In the current study, we aimed to investigate the effect of paeoniflorin on autoimmune myocarditis. A total of 72 young Lewis rats were randomly divided into control, experimental autoimmune myocarditis (EAM), paeoniflorin low dose (Pae-L 20 mg/kg), paeoniflorin high dose (Pae-H, 40 mg/kg), EAM-NC, CXCR5 siRNA groups, respectively. The levels of TNF-α, IL-6, IFN-γ, and IL-21 were detected. H&E staining was used to investigate the histopathological changes of myocardial tissue. Flow cytometry and immunofluorescence double-labeling assay were used to detect the CD4 and CXCR5. Western blot was employed to investigate the expression of proteins. Pae enhanced the body weight and ameliorated the histopathology and inflammation score of myocardial tissue on day 21 and 35. In the peripheral blood, Pae diminished the proportion of CD4 + CXCR5 + Tfh cells on day 21 and day 35. Furthermore, Pae decreased the expression of CXCR5, CXCL13, programmed cell death-1 (PD-1), phosphorylated p38 (p-p38), phosphorylated ERK1/2 (p-ERK1/2), Bcl-6, and Inducible T cell CO-Stimulator (ICOS) in myocardial tissue on day 35. Our study indicated that paeoniflorin could effectively alleviate autoimmune myocarditis. The mechanism is possibly related to inhibit CXCR5 to reduce Tfh cells via p38 MAPK signaling.