题　目：

Role of suppressor of cytokine signalling (SOCS) proteins in antiviral immunity and control of inflammation

主讲人：

Lukasz Kedzierski

主持人：

王忠芳 教授

时　间：

2019年10月15日（星期二）下午15:00-16:00

地　点：

广州医科大学越秀校区16号楼五楼第一会议室

讲座内容：

SOCS proteins are negative regulators of cytokine signalling. Prototypical SOCS1-3, CIS have defined functions, however, SOCS4 and 5 have no described biological role. We have investigated the role SOCS4 and SOCS5 during viral infection. Using murine influenza model, we have demonstrated that lack of SOCS4 leads to greater susceptibility to infection, linked to delayed viral clearance and impaired trafficking of influenza specific CD8+ T cells. Given the similarity between SOCS4 and 5, we have postulated that SOCS5 also plays a role in infection. In contrast to Socs4-deficient mice, lack of SOCS5 led to differences early in infection, suggesting that the innate immune response is perturbed. An intrinsic defect in epithelial cells was confirmed by infection of Socs5-/- primary lung epithelial cells, and bone marrow chimeras. These data are the first demonstration of a functional phenotype for SOCS4- and SOCS5-deficient mice and suggests that both proteins play a role in immune regulation during viral infection. To further investigate the role of both proteins we used a model of viral encephalitis and demonstrated that lack of either SOCS4 or SOCS5 changes the susceptibility to neurotropic infection with Semliki Forest virus. SOCS4-deficeint mice showed accelerated viral clearance and reduction in viral RNA accompanied by increased inflammatory infiltration and severe histopathology in the brain. SOCS5 knockout mice display exacerbated weight loss, overall dysregulation in cytokine production followed by a significantly greater inflammatory infiltrate. These results demonstrate that SOCS4 and SOCS5 are critical regulators of anti-viral immunity in the CNS.

主讲人介绍：

Dr Lukasz Kedzierski completed his PhD at Monash University, where he tested efficacy of a novel malaria vaccine antigen in a murine model of infection. Subsequently, he moved to the Walter and Eliza Hall Institute where he worked on the protozoan parasite Leishmania. His projects involved investigation of host-parasite interactions, drug discovery and anti-parasite immunity. He then shifted his focus to investigate the role of suppressors of cytokine signalling during viral infection. In 2017, Lukasz moved to the Peter Doherty Institute for Infection and Immunity. His current work focuses on understanding the immune mechanisms during viral encephalitis and the role of SOCS in viral infections. Lukasz was awarded an NHMRC Peter Doherty Postdoctoral Fellowship, NHMRC Project Grants and ARC Discovery grants. He presented his work at numerous national and international conferences and his work was published in journals such as Plos Pathogens, eLIFE, Nature Communications and PNAS. His work on the role of SOCS in influenza was featured in Australian daily newspapers (Herald Sun, Advertiser, Courier Mail) and online portals (Science Daily, Medical News Today).

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呼吸疾病国家重点实验室

广州呼吸健康研究院

国家呼吸系统疾病临床医学研究中心

广州医科大学附属第一医院

2019年10月12日