调控Gal-9/Tim-3通路对小鼠胶原诱导性关节炎作用的研究

被引:4
作者
杨骁
彭昊
周建林
方洪松
陈森
机构
[1] 武汉大学人民医院骨科
关键词
类风湿性关节炎; 胶原诱导性关节炎; 辅助性T细胞; 调节性T细胞; 信号通路;
D O I
暂无
中图分类号
R593.22 [类风湿性关节炎];
学科分类号
1002 ; 100201 ;
摘要
目的探讨激活或阻断Gal-9/Tim-3信号通路对小鼠胶原诱导性关节炎的影响及其机制。方法 6~8周龄雌性BALB/c小鼠30只,建立Ⅱ型胶原诱导性关节炎模型,造模后第7天加强免疫。于加强免疫前1 d随机分为激活组、阻断组、对照组,每组10只,分别经尾静脉输注半乳糖凝集素-9(Gal-9)、阻断剂Tim-3单抗、PBS。造模后28d观察三组小鼠踝关节变形程度,记录关节炎指数,ELISA法检测血清抗炎因子白介素-10(IL-10)、转化生长因子β(TGF-β)水平,RT-PCR检测踝关节滑膜组织辅助性T细胞(Th17)、调节性T细胞(Treg)标志性蛋白ROR-γt、Fox P3表达量。结果加强免疫后,三组小鼠出现不同程度关节变形,造模后第28天关节炎指数:激活组为(7.12±1.53)分、阻断组为(13.82±2.12)分、对照组为(10.88±1.84)分,差异有高度统计学意义(P<0.01);血清IL-10、TGF-β水平:激活组[(12.88±2.23)、(27.61±4.52)ng/L]明显高于对照组[(7.49±1.70)、(21.33±2.07)ng/L](P<0.01),阻断组[(4.26±1.79)、(12.35±2.42)ng/L]明显低于对照组(P<0.01);RT-PCR结果显示:ROR-γt m RNA在滑膜组织的表达情况激活组明显低于对照组(P<0.01),阻断组明显高于对照组(P<0.01);Fox P3 m RNA表达情况激活组明显高于对照组(P<0.01),阻断组明显低于对照组(P<0.01)。结论激活Gal-9/Tim-3通路可缓解小鼠胶原诱导性关节炎,阻断该通路则加重炎性反应,作用机制可能与该通路抑制Th17,活化Treg有关。
引用
收藏
页码:4 / 7
页数:4
相关论文
共 11 条
[1]   Th17/Treg平衡在类风湿关节炎发病和治疗中的意义 [J].
张莹 ;
周小莉 .
中国医药导报, 2015, 12 (24) :48-52
[2]   类风湿关节炎动物模型与临床的关系 [J].
张玲玲 ;
沈玉先 ;
魏伟 .
中国药理学通报, 2002, (05) :502-506
[3]  
Regulation of T cell responses by the receptor molecule Tim-3[J] . Jacob V. Gorman,John D. Colgan. Immunologic Research . 2014 (1-3)
[4]  
Therapeutic targets for rheumatoid arthritis: Progress and promises[J] . Abdullah Alghasham,Zafar Rasheed. Autoimmunity . 2014 (2)
[5]   The Tim-3/galectin-9 pathway involves in the homeostasis of hepatic Tregs in a mouse model of concanavalin A-induced hepatitis [J].
Ju, Ying ;
Shang, Xuming ;
Liu, Zhanfeng ;
Zhang, Ji ;
Li, Yuantang ;
Shen, Yajuan ;
Liu, Yiqing ;
Liu, Chunmei ;
Liu, Bin ;
Xu, Liyun ;
Wang, Yong ;
Zhang, Bingchang ;
Zou, Jianwen .
MOLECULAR IMMUNOLOGY, 2014, 58 (01) :85-91
[6]  
Genome-wide association studies to advance our understanding of critical cell types and pathways in rheumatoid arthritis: recent findings and challenges[J] . Dorothée Diogo,Yukinori Okada,Robert M. Plenge. Current Opinion in Rheumatology . 2014 (1)
[7]   Altered Th17 cells and Th17/regulatory T-cell ratios indicate the subsequent conversion from undifferentiated connective tissue disease to definitive systemic autoimmune disorders [J].
Szodoray, Peter ;
Nakken, Britt ;
Barath, Sandor ;
Csipo, Istvan ;
Nagy, Gabor ;
El-Hage, Fadi ;
Osnes, Liv T. ;
Szegedi, Gyula ;
Bodolay, Edit .
HUMAN IMMUNOLOGY, 2013, 74 (12) :1510-1518
[8]   Dysregulated Tim-3 expression and its correlation with imbalanced CD4 helper T cell function in ulcerative colitis [J].
Shi, Fengmin ;
Guo, Xiaoqin ;
Jiang, Xingwei ;
Zhou, Ping ;
Xiao, Yan ;
Zhou, Tingting ;
Chen, Guojiang ;
Zhao, Zhi ;
Xiao, He ;
Hou, Chunmei ;
Li, Xinying ;
Yang, Xiaomei ;
Wang, Renxi ;
Feng, Jiannan ;
Shen, Beifen ;
Li, Yan ;
Han, Gencheng .
CLINICAL IMMUNOLOGY, 2012, 145 (03) :230-240
[9]   The impaired immune regulation of autoimmune hepatitis is linked to a defective galectin-9/tim-3 pathway [J].
Liberal, Rodrigo ;
Grant, Charlotte R. ;
Holder, Beth S. ;
Ma, Yun ;
Mieli-Vergani, Giorgina ;
Vergani, Diego ;
Longhi, Maria Serena .
HEPATOLOGY, 2012, 56 (02) :677-686
[10]  
Involvement of T cell Ig Mucin-3 (Tim-3) in the negative regulation of inflammatory bowel disease[J] . Xia Li,Guojiang Chen,Yurong Li,Renxi Wang,Liyan Wang,Zhou Lin,Xudong Gao,Jiannan Feng,Yuanfang Ma,Beifen Shen,Yan Li,Gencheng Han. Clinical Immunology . 2009 (2)