Th1 Biased Progressive Autoimmunity in Aged Aire-Deficient Mice Accelerated Thymic Epithelial Cell Senescence

被引:7
|
作者
Zhang, Jie [1 ]
Wang, Yuqing [1 ]
Aili, Abudureyimujiang [1 ]
Sun, Xiuyuan [1 ]
Pang, Xuewen [1 ]
Ge, Qing [1 ]
Zhang, Yu [1 ]
Jin, Rong [1 ]
机构
[1] Peking Univ, Minist Hlth, Key Lab Med Immunol, Dept Immunol,Sch Basic Med Sci,Hlth Sci Ctr, Beijing 100191, Peoples R China
来源
AGING AND DISEASE | 2019年 / 10卷 / 03期
基金
北京市自然科学基金;
关键词
Aire; thymic senescence; thymic epithelial cells; autoimmune disease; Th1; SYSTEMIC-LUPUS-ERYTHEMATOSUS; T-CELL; IFN-GAMMA; INTERFERON-GAMMA; INVOLUTION; EXPANSION; MEDULLA;
D O I
10.14336/AD.2018.0608
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Although autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, are frequently associated with premature aging of the thymus, a direct link is missing between autoimmunity and thy mic atrophy. Here we monitored the progression of thy mic involution in Aire-deficient mice, in which defective negative selection causes spontaneous and progressive development of autoimmunity. In young and middle-aged mice, Aire deficiency appeared to be protective as supported by the reduced beta-gal(+) epithelial cells and the enhanced thy mic output. However, once the autoimmune phenotype was fully developed in aged Aire-deficient mice, their thymuses underwent accelerated involution. In comparison to the age-matched w ildtype littermates, old Aire-deficient mice showed lower numbers of total thymocytes and recent thy mic emigrants but more beta-gal(+) thymic epithelial cells. This phenomenon may partly be attributable to the increased number of activated Th1 cells homing to the thymus. This speculation was further supported by the enhanced thy mic aging following repeated challenges with complete Freund's adjuvant immunization. Taken together, the present study highlights a unique mechanism by which autoimmunity facilitates the senescence of thy mic epithelial cells through returning Th1 cells.
引用
收藏
页码:497 / 509
页数:13
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