| First Author | Zuo D | Year | 2013 |
| Journal | Hepatology | Volume | 57 |
| Issue | 1 | Pages | 228-38 |
| PubMed ID | 22821642 | Mgi Jnum | J:310445 |
| Mgi Id | MGI:6762938 | Doi | 10.1002/hep.25983 |
| Citation | Zuo D, et al. (2013) Scavenger receptor A restrains T-cell activation and protects against concanavalin A-induced hepatic injury. Hepatology 57(1):228-38 |
| abstractText | UNLABELLED: 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-gamma 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. |
