GDF15 alleviates the severity of experimental autoimmune myocarditis by inhibiting B cells function

Growth differentiation factor 15 (GDF15) is a novel biomarker of cardiovascular disease progression that has gained attention for its role in energy homeostasis. The current study investigated the role of GDF15 in myocarditis using experimental autoimmune myocarditis (EAM) mouse model through intraperitoneal injection of recombinant mouse GDF15 protein (rmGDF15) and tail vein injection of adeno-associated virus 9 encoding shRNA targeting GDF15 (AAV9-GDF15-shRNA) to knockdown GDF15 expression. The results showed that GDF15 expression was elevated in the cardiac tissue of EAM mice, and rmGDF15 treatment significantly decreased cardiac inflammation and improved cardiac function in EAM mice. Furthermore, rmGDF15 attenuated cardiac B cells infiltration, reduced serum IgG and IgM expression, and inhibited cardiac TNF-α and IL-6 expression. Knockdown of GDF15 using AAV9-GDF15-shRNA exacerbated the severity of EAM, increased the proportion of B cells in the heart of EAM mice. In vitro, GDF15 inhibited lipopolysaccharide (LPS)-induced B cell activation, plasma cells differentiation. We further explore the mechanism of GDF15 in B cell function. It showed that GDF15 down-regulated the expressions of autophagy related proteins including P62, Beclin1, LC3B II/I and reactive oxygen species (ROS) production in B cells. In conclusion, our data suggested that GDF15 alleviated EAM severity by suppressing B cells function.