CD70 contributes to age-associated T cell defects and overwhelming inflammatory responses
CD70 contributes to age-associated T cell defects and overwhelming inflammatory responses
复制标题
DOI：
10.18632/aging.103368
复制
发表时间：
2020-05
期刊：
影响因子：
--
通讯作者：
Di Wang;Juan Du;Yangzi Song;Beibei Wang;Rui Song;Y. Hao;Yongqin Zeng;Jiang Xiao;Hong Zheng;H. Zeng;Hongxin Zhao;Y. Kong
中科院分区：
文献类型：
--
作者：
Di Wang;Juan Du;Yangzi Song;Beibei Wang;Rui Song;Y. Hao;Yongqin Zeng;Jiang Xiao;Hong Zheng;H. Zeng;Hongxin Zhao;Y. Kong
衰老与免疫失调有关，尤其是T细胞紊乱，导致对各种疾病的易感性增加。先前的研究表明，共刺激受体的缺失或共抑制分子的积累在T细胞衰老中起重要作用。本研究发现，通常被认为是共刺激分子的CD70在老年人CD4+和CD8+ T细胞中表达上调。衰老的CD70+ T细胞表现出过度激活的表型，并表达了多种抑制受体，包括PD-1、2B4和LAG-3。老年个体的CD70+ T细胞表现出更高的凋亡敏感性和高水平的炎症细胞因子。重要的是，通过阻断CD70，与衰老相关的CD70+ T细胞的功能失调被逆转。总的来说，本研究证明CD70是一个重要的调节因子，参与免疫衰老，导致T细胞在衰老过程中出现缺陷和压倒性的炎症反应。这些发现为靶向CD70预防与免疫衰老相关的失调提供了强有力的理论依据。
Aging is associated with immune dysregulation, especially T cell disorders, which result in increased susceptibility to various diseases. Previous studies have shown that loss of co-stimulatory receptors or accumulation of co-inhibitory molecules play important roles in T cell aging. In the present study, CD70, which was generally regarded as a costimulatory molecule, was found to be upregulated on CD4+ and CD8+ T cells of elderly individuals. Aged CD70+ T cells displayed a phenotype of over-activation, and expressed enhanced levels of numerous inhibitory receptors including PD-1, 2B4 and LAG-3. CD70+ T cells from elderly individuals exhibited increased susceptibility to apoptosis and high levels of inflammatory cytokines. Importantly, the functional dysregulation of CD70+ T cells associated with aging was reversed by blocking CD70. Collectively, this study demonstrated CD70 as a prominent regulator involved in immunosenescence, which led to defects and overwhelming inflammatory responses of T cells during aging. These findings provide a strong rationale for targeting CD70 to prevent dysregulation related to immunosenescence.