AUTHOR=Li Xiaying , Liu Yanan , Wang Yongqiang , Liu Jue , Li Xiaoqi , Cao Hong , Gao Xiang , Zheng Shijun J. TITLE=Negative Regulation of Hepatic Inflammation by the Soluble Resistance-Related Calcium-Binding Protein via Signal Transducer and Activator of Transcription 3 JOURNAL=Frontiers in Immunology VOLUME=8 YEAR=2017 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00709 DOI=10.3389/fimmu.2017.00709 ISSN=1664-3224 ABSTRACT=

Host immune response is tightly controlled by negative regulators to avoid excessive immune reactions for homeostasis. Some pathogens may take advantage of host negative regulating system to evade host defense. Our previous report showed that foot-and-mouth disease virus (FMDV) VP1 inhibited TNF-α- and SeV-induced type I interferon response via interaction with cellular protein soluble resistance-related calcium-binding protein (sorcin). Conversely, TNF-α- or SeV-induced type I interferon response increased when sorcin knocked down, leading to inhibition of vesicular stomatitis virus replication. However, the exact role of sorcin in regulation of the immune response is still not clear. Here, we show that mice deficient of sorcin (sorcin−/−) display enhanced ConA-induced hepatitis. Importantly, splenocytes from sorcin−/− mice produced more IL-2, IL-4, IL-17, and IFN-γ than that of littermate controls (sorcin+/+) in response to anti-CD3/28 stimulation. Furthermore, our data indicate that sorcin interacts with signal transducer and activator of transcription 3 (STAT3) and enhances its phosphorylation and that STAT3 acts as an immediate downstream molecule of sorcin in the negative regulation of NF-κB signaling. Thus, sorcin, in association with STAT3, negatively regulates hepatic inflammation.