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

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

  • Biochem Biophys Res Commun. 2025 Nov 28:791:152920. doi: 10.1016/j.bbrc.2025.152920.
Wenjing Tang 1,  Shijun Yang 2,  Shuang Wen 3,  Ran Gao 2,  Peiwu Ding 2,  Xiaoying Gu 3,  Xiao Liu 2,  Wei Liang 4,  Miao Yu 5
Affiliations

Affiliations

  • 1 Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Diabetes and Metabolic Disease Clinical Research Center of Hubei Province, China; Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, China; Hubei Branch of National Center for Clinical Medical Research of Metabolic Diseases, China.
  • 2 Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
  • 3 Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4 Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China. Electronic address: [email protected].
  • 5 Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China. Electronic address: [email protected].
PMID: 41232385 DOI: 10.1016/j.bbrc.2025.152920
Abstract

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.

Keywords

Autophagy; B cells; Experimental autoimmune myocarditis; Growth differentiation factor-15.

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