Egr2 and 3 control inflammation, but maintain homeostasis, of PD-1high memory phenotype CD4 T cells
Egr2 and 3 control inflammation, but maintain homeostasis, of PD-1high memory phenotype CD4 T cells
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Egr2和3控制炎症，但维持PD-1高记忆表型CD4 T细胞的稳态
DOI：
10.26508/lsa.202000766
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发表时间：
2020-09-01
影响因子：
4.4
通讯作者：
Wang, Ping
中科院分区：
文献类型：
--
作者：
Symonds, Alistair L. J.;Zheng, Wei;Wang, Ping
转录因子Egr 2和3对于控制记忆表型（MP）CD 4 T细胞的炎性自身免疫应答是必不可少的。然而，其机制尚不清楚。我们现在已经发现MP CD 4 T细胞的Egr 2（+）亚群（PD-1（高）MP）表达高水平的检查点分子（PD-1和Lag 3）以及效应T细胞的标志物（CXCR 3和ICAM-1）。Egr 2/3不是PD-1（高）MP CD 4细胞发育所必需的，但介导一种独特的转录程序，可有效控制其炎症反应，同时促进稳态增殖和适应性反应。Egr 2阴性PD-1（高）MP CD 4 T细胞在稳态增殖和针对病毒感染的适应性应答中受损，但对先天刺激（如IL-12）显示出炎症应答。PD-1（高）MP CD 4 T细胞最近被认为与类风湿性关节炎发病机制有关，我们现在发现，与健康对照相比，活动性类风湿性关节炎患者的PD-1（高）MP CD 4 T细胞中Egr 2表达减少。这些发现表明，Egr 2/3控制PD-1（高）MP CD 4 T细胞的炎症反应，并维持其适应性免疫适应性。
The transcription factors Egr2 and 3 are essential for controlling inflammatory autoimmune responses of memory phenotype (MP) CD4 T cells. However, the mechanism is still unclear. We have now found that the Egr2(+) subset (PD-1(high) MP) of MP CD4 T cells expresses high levels of checkpoint molecules (PD-1 and Lag3) and also markers of effector T cells (CXCR3 and ICAM-1). Egr2/3 are not required for PD-1(high) MP CD4 cell development but mediate a unique transcriptional programme that effectively controls their inflammatory responses, while promoting homeostatic proliferation and adaptive responses. Egr2 negative PD-1(high) MP CD4 T cells are impaired in homeostatic proliferation and adaptive responses against viral infection but display inflammatory responses to innate stimulation such as IL-12. PD-1(high) MP CD4 T cells have recently been implicated in rheumatoid arthritis pathogenesis, and we have now found that Egr2 expression is reduced in PD-1(high) MP CD4 T cells from patients with active rheumatoid arthritis compared with healthy controls. These findings demonstrate that Egr2/3 control the inflammatory responses of PD-1(high) MP CD4 T cells and maintain their adaptive immune fitness.