Endogenous n-3 Polyunsaturated Fatty Acids Attenuate T Cell-Mediated Hepatitis via Autophagy Activation.
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert anti-inflammatory effects in several liver disorders, including cirrhosis, acute liver failure, and fatty liver disease. To date, little is known about their role in immune-mediated liver diseases. In this study, we used fat-1 transgenic mice rich in endogenous n-3 PUFAs to examine the role of n-3 PUFAs in immune-mediated liver injury. Concanavalin A (Con A) was administered intravenously to wild-type (WT) and fat-1 transgenic mice to induce T cell-mediated hepatitis. Reduced liver damage was shown in Con A-administrated fat-1 transgenic mice, as evidenced by decreased mortality, attenuated hepatic necrosis, lessened serum alanine aminotransferase activity, and inhibited production of pro-inflammatory cytokines (e.g., TNF-α, IL-6, IL-17A, and IFN-γ). In vivo and in vitro studies demonstrated that n-3 PUFAs significantly inhibited the activation of hepatic T cells and the differentiation of Th1 cells after Con A challenge. Further studies showed that n-3 PUFAs markedly increased autophagy level in Con A-treated fat-1 T cells compared with the WT counterparts. Blocking hepatic autophagy activity with chloroquine diminished the differences in T cell activation and liver injury between Con A-injected WT and fat-1 transgenic mice. We conclude that n-3 PUFAs limit Con A-induced hepatitis via an autophagy-dependent mechanism and could be exploited as a new therapeutic approach for autoimmune hepatitis.
Department of Immunology, School of Basic Medical Sciences, Southern Medical University , Guangzhou , China.
Yanli
Y
Li
Department of Immunology, School of Basic Medical Sciences, Southern Medical University , Guangzhou , China.
Yuan
Y
Tang
Department of Immunology, School of Basic Medical Sciences, Southern Medical University , Guangzhou , China.
Shoujie
S
Wang
Department of Immunology, School of Basic Medical Sciences, Southern Medical University , Guangzhou , China.
Jing
J
Zhou
Department of Immunology, School of Basic Medical Sciences, Southern Medical University , Guangzhou , China.
Jia
J
Zhou
Department of Immunology, School of Basic Medical Sciences, Southern Medical University , Guangzhou , China.
Xiao
X
Lu
Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University , Guangzhou , China.
Xiaochun
X
Bai
Department of Human Molecular Genetics, Virginia Commonwealth University , Richmond, VA , USA.
Xiang-Yang
XY
Wang
Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China; Guangdong Province Key Laboratory of Proteomics, Southern Medical University, Guangzhou, China.
Zhengliang
Z
Chen
Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China; State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Daming
D
Zuo
T cell activation; autophagy; concanavalin A-induced hepatitis; immune-mediated liver injury; omega-3 polyunsaturated fatty acids
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