TY - JOUR
T1 - B cells are indispensable for a novel mouse model of primary Sjögren's syndrome
AU - Zheng, Junfeng
AU - Huang, Qiaoniang
AU - Huang, Renliang
AU - Deng, Fengyuan
AU - Yue, Xiaoyang
AU - Yin, Junping
AU - Zhao, Wenjie
AU - Chen, Yan
AU - Wen, Lifang
AU - Zhou, Jun
AU - Huang, Renda
AU - Riemekasten, Gabriela
AU - Liu, Zuguo
AU - Petersen, Frank
AU - Yu, Xinhua
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China (No.81371325 and No. 81571593), the Deutsche Forschungsgemeinschaft, GRK1727 ''Modulation of Autoimmunity'' and the German Center for Lung Research (DZL).
Publisher Copyright:
© 2017 Zheng, Huang, Huang, Deng, Yue, Yin, Zhao, Chen, Wen, Zhou, Huang, Riemekasten, Liu, Petersen and Yu.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/10/24
Y1 - 2017/10/24
N2 - Primary Sjögren's syndrome (pSS) is characterized by a panel of autoantibodies, while it is not clear whether B cells and autoantibodies play an essential role in pathogenesis of the disease. Here, we report a novel mouse model for pSS which is induced by immunization with the Ro60_316-335 peptide containing a predominant T cell epitope. After immunization, mice developed several symptoms mimicking pSS, including a decreased secretion of tears, lymphocytic infiltration into the lacrimal glands, autoantibodies, and increased levels of inflammatory cytokines. Disease susceptibility to this novel mouse model varies among strains, where C3H/HeJ (H2-k) and C3H/HeN (H2-k) are susceptible while DBA/1 (H2-q) and C57BL/6 (H2-b) are resistant. Depletion of B cells using anti-CD20 monoclonal antibodies prevented C3H/HeN mice from development of the pSS-like disease. In addition, HLA-DRB1*0803, a pSS risk allele, was predicted to bind to the hRo60_308-328 which contains a predominant T cell epitope of human Ro60. Therefore, this study provides a novel mouse model for pSS and reveals an indispensable role of B cells in this model. Moreover, it suggests that T cell epitope within Ro60 antigen is potentially pathogenic for pSS.
AB - Primary Sjögren's syndrome (pSS) is characterized by a panel of autoantibodies, while it is not clear whether B cells and autoantibodies play an essential role in pathogenesis of the disease. Here, we report a novel mouse model for pSS which is induced by immunization with the Ro60_316-335 peptide containing a predominant T cell epitope. After immunization, mice developed several symptoms mimicking pSS, including a decreased secretion of tears, lymphocytic infiltration into the lacrimal glands, autoantibodies, and increased levels of inflammatory cytokines. Disease susceptibility to this novel mouse model varies among strains, where C3H/HeJ (H2-k) and C3H/HeN (H2-k) are susceptible while DBA/1 (H2-q) and C57BL/6 (H2-b) are resistant. Depletion of B cells using anti-CD20 monoclonal antibodies prevented C3H/HeN mice from development of the pSS-like disease. In addition, HLA-DRB1*0803, a pSS risk allele, was predicted to bind to the hRo60_308-328 which contains a predominant T cell epitope of human Ro60. Therefore, this study provides a novel mouse model for pSS and reveals an indispensable role of B cells in this model. Moreover, it suggests that T cell epitope within Ro60 antigen is potentially pathogenic for pSS.
UR - http://www.scopus.com/inward/record.url?scp=85032222810&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2017.01384
DO - 10.3389/fimmu.2017.01384
M3 - Journal articles
AN - SCOPUS:85032222810
SN - 1664-3224
VL - 8
JO - Frontiers in Immunology
JF - Frontiers in Immunology
IS - OCT
M1 - 1384
ER -