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Scavenger receptor a restrains T‐cell activation and protects against concanavalin A‐induced hepatic injury
Author(s) -
Zuo Daming,
Yu Xiaofei,
Guo Chunqing,
Wang Hongxia,
Qian Jie,
Yi Huanfa,
Lu Xiao,
Lv ZhiPing,
Subjeck John R.,
Zhou Huiping,
Sanyal Arun J.,
Chen Zhengliang,
Wang XiangYang
Publication year - 2013
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.25983
Subject(s) - liver injury , scavenger receptor , immune system , t cell , immunology , hepatic stellate cell , adoptive cell transfer , concanavalin a , biology , autoimmune hepatitis , hepatitis , medicine , endocrinology , lipoprotein , biochemistry , cholesterol , in vitro
Abstract Negative feedback immune mechanisms are essential for maintenance of hepatic homeostasis and prevention of immune‐mediated liver injury. We show here that scavenger receptor A (SRA/CD204), a pattern recognition molecule, is highly up‐regulated in the livers of patients with autoimmune or viral hepatitis, and of mice during concanavalin A (Con A)‐induced hepatitis (CIH). Strikingly, genetic SRA ablation strongly sensitizes mice to Con A‐induced liver injury. SRA loss, increased mortality and liver pathology correlate with excessive production of IFN‐γ and heightened activation of T cells. Increased liver expression of SRA primarily occurs in mobilized hepatic myeloid cells during CIH, including CD11b + Gr‐1 + cells. Mechanistic studies establish that SRA on these cells functions as a negative regulator limiting T‐cell activity and cytokine production. SRA‐mediated protection from CIH is further validated by adoptive transfer of SRA + hepatic mononuclear cells or administration of a lentivirus‐expressing SRA, which effectively ameliorates Con A‐induced hepatic injury. Also, CIH and clinical hepatitis are associated with increased levels of soluble SRA. This soluble SRA displays a direct T‐cell inhibitory effect and is capable of mitigating Con A‐induced liver pathology. Conclusion : Our findings demonstrate an unexpected role of SRA in attenuation of Con A‐induced, T‐cell‐mediated hepatic injury. We propose that SRA serves as an important negative feedback mechanism in liver immune homeostasis, and may be exploited for therapeutic treatment of inflammatory liver diseases. (H EPATOLOGY 2013)