Common genetic heterogeneity of human interleukin-37 leads to functional variance

作     者：Jingjing Yan Yuling Zhang Shimeng Cheng Bin Kang Jinbiao Peng Xiaodan Zhang Meichun Yuan Wenqi Chu Wen Zhang Jiayin Shen Shuye Zhang 

作者机构：Shanghai Public Health Clinical Center and Institutes of Biomedical SciencesFudan UniversityShanghaiChina School of Life SciencesHebei Normal UniversityShi-JiazhuangHebei Key Laboratory of Medical Molecular Virology of Ministries of Education/HealthInstitute of Medical MicrobiologyShanghai Medical College of Fudan UniversityShanghaiChina 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2017年第14卷第9期

页      面：783-791页

核心收录：

学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by grants from the National Natural Science Foundation of China(No.81371823 to SZ and No.31500697 to JS) the 973 Project(No.2015CB554300 to SZ) the Shanghai Pujiang Program(No.15PJ1407300 to JS) 

主　　题：Cytokine gene variation inflammation protein stability 

摘      要：Interleukin-37(IL-37)is an inhibitory member of the IL-1 family of *** previously found that balanced selection maintains common variations of the human IL37 ***,the functional consequences of this selection have yet to be ***,using cells expressing exogenous IL-37 variants,including IL-37 Ref and IL-37 Var1 and Var2,we found that the three variants of IL-37 exhibited different immunoregulatory potencies in response to immune *** protein level of IL-37 Var2 was found to be significantly less than that of IL-37 Ref or Var1,despite the comparable mRNA levels of all three *** study showed that IL-37 Var2 was rapidly degraded by a proteasome-dependent mechanism mediated by enhanced polyubiquitination,leading to a transient upregulation of IL-37 Var2 after immune ***,when ectopically expressed in cells,human IL-37 Var2 exerted less inhibition on proinflammatory cytokine production than did other IL-37 ***,purified extracellular IL-37 variant proteins demonstrated comparable inhibitory abilities in *** conclusion,our study reveals that common genetic variants of IL37 lead to different immune-inhibitory potencies,primarily as a result of differences in IL-37 protein stability,suggesting the possible involvement of these variants in various human diseases.