Proteomic analysis reveals distinctive protein profiles involved in CD8^(+) T cell-mediated murine autoimmune cholangitis

作     者：Weici Zhang Ren Zhang Jun Zhang Ying Sun Patrick SC Leung Guo-Xiang Yang Zongwen Shuai William M Ridgway M Eric Gershwin 

作者机构：Division of RheumatologyAllergy and Clinical ImmunologyUniversity of CaliforniaDavisCaliforniaUSA Department of Pathogenic Biology and ImmunologyGuangzhou University of Chinese MedicineGuangzhou 510006China Center for non-infectious liver diseasesBeijing 302 HospitalBeijing 100039China Department of Rheumatology and ImmunologyThe First Affiliated Hospital of Anhui Medical UniversityHefei 230022China Division of ImmunologyAllergy and RheumatologyUniversity of CincinnatiCincinnatiOH 45267 

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

年 卷 期：2018年第15卷第8期

页      面：756-767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：Funded by National Institutes of Health grant DK090019. 

主　　题：autoimmune cholangitis CD8 dnTGFβRII mice proteomic analysis 

摘      要：Autoimmune cholangitis arises from abnormal innate and adaptive immune responses in the liver,and T cells are critical drivers in this process.However,little is known about the regulation of their functional behavior during disease development.We previously reported that mice with T cell-restricted expression of a dominant negative form of transforming growth factor beta receptor type Ⅱ(dnTGFβ RII)spontaneously develop an autoimmune cholangitis that resembles human primary biliary cholangitis(PBC).Adoptive transfer of CD8^(+) but not CD4^(+) T cells into Rag1^(−/−)mice reproduced the disease,demonstrating a critical role for CD8^(+) T cells in PBC pathogenesis.Herein,we used SOMAscan technology to perform proteomic analysis of serum samples from dnTGFβRII and B6 control mice at different ages.In addition,we analyzed CD8 protein profiles after adoptive transfer of splenic CD8^(+) cells into Rag1^(−/−)recipients.The use of the unique SOMAscan aptamer technology revealed critical and distinct profiles of CD8 cells,which are key to biliary mediation.In total,254 proteins were significantly increased while 216 proteins were significantly decreased in recipient hepatic CD8^(+) cells compared to donor splenic CD8^(+) cells.In contrast to donor splenic CD8^(+) cells,recipient hepatic CD8^(+) cells expressed distinct profiles for proteins involved in chemokine signaling,focal adhesion,T cell receptor and natural killer cell-mediated cytotoxicity pathways.