CD70-induced differentiation of proinflammatory Th1/17/22/GM lymphocytes associated with disease progression and immune reconstitution during HIV infection.
CD70-induced differentiation of proinflammatory Th1/17/22/GM lymphocytes associated with disease progression and immune reconstitution during HIV infection.
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DOI：
10.1080/22221751.2023.2271068
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发表时间：
2023-12
影响因子：
13.2
通讯作者：
Kong, Yaxian
中科院分区：
文献类型：
--
作者：
Wang, Xinyue;Wei, Yuqing;He, Zhijiao;Wang, Di;Zhang, Leidan;Du, Juan;Zhang, Mengyuan;Jiang, Meiqing;Chen, Na;Deng, Meiju;Li, Bei;Song, Chuan;Chen, Danying;Liu, Huan;Xiao, Jiang;Liang, Hongyuan;Zhao, Hongxin;Kong, Yaxian
免疫过度激活是慢性HIV感染的一个标志，对HIV发病和疾病进展至关重要。辅助性T细胞（Th）分化的不平衡和随后的细胞因子失调通常被认为是HIV感染中过度活化和炎性疾病的主要驱动因素。然而，驱动HIV相关Th变化的准确因素仍有待确定。CD 70是一种共刺激分子，在HIV感染过程中，CD 4 + T细胞上的CD 70增加。最近报道，CD 4 + T细胞上CD 70的过表达与多发性硬化症中的高致病性促炎性Th 1/Th 17极化相关。因此，CD 70在HIV感染过程中Th极化失衡和免疫过度激活中的作用需要研究。在这里，我们发现CD 70 + CD 4 + T细胞的频率升高与CD 4计数呈负相关，与未经治疗的HIV感染者（PLWH）的免疫激活呈正相关。更重要的是，CD 70表达定义了PLWH中促炎性Th 1/17/22/GM亚群的群体。阻断CD 70可降低Th 1/17/22/GM极化过程中亚群特异性标志物的mRNA表达。此外，我们还证实了CD 70通过STAT途径影响这些Th细胞的分化。最后，研究发现，CD 4 + T细胞上CD 70基线水平高的患者在抗逆转录病毒治疗（ART）后免疫重建不良的风险高于CD 70低的患者。总的来说，我们的数据强调了CD 70在HIV感染期间Th 1/17/22/GM分化中的作用，并为CD 70作为预测免疫恢复的潜在生物标志物提供了证据。
Immune overactivation is a hallmark of chronic HIV infection, which is critical to HIV pathogenesis and disease progression. The imbalance of helper T cell (Th) differentiation and subsequent cytokine dysregulation are generally considered to be the major drivers of excessive activation and inflammatory disorders in HIV infection. However, the accurate factors driving HIV-associated Th changes remained to be established. CD70, which was a costimulatory molecule, was found to increase on CD4+ T cells during HIV infection. Overexpression of CD70 on CD4+ T cells was recently reported to associate with highly pathogenic proinflammatory Th1/Th17 polarization in multiple sclerosis. Thus, the role of CD70 in the imbalance of Th polarization and immune overactivation during HIV infection needs to be investigated. Here, we found that the elevated frequency of CD70 + CD4+ T cells was negatively correlated with CD4 count and positively associated with immune activation in treatment-naïve people living with HIV (PLWH). More importantly, CD70 expression defined a population of proinflammatory Th1/17/22/GM subsets in PLWH. Blocking CD70 decreased the mRNA expression of subset-specific markers during Th1/17/22/GM polarization. Furthermore, we demonstrated that CD70 influenced the differentiation of these Th cells through STAT pathway. Finally, it was revealed that patients with a high baseline level of CD70 on CD4+ T cells exhibited a greater risk of poor immune reconstitution after antiretroviral therapy (ART) than those with low CD70. In general, our data highlighted the role of CD70 in Th1/17/22/GM differentiation during HIV infection and provided evidence for CD70 as a potential biomarker for predicting immune recovery.
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DOI：
10.1084/jem.20070663
发表时间：
2007-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Annunziato F;Cosmi L;Santarlasci V;Maggi L;Liotta F;Mazzinghi B;Parente E;Filì L;Ferri S;Frosali F;Giudici F;Romagnani P;Parronchi P;Tonelli F;Maggi E;Romagnani S
通讯作者：
Romagnani S
Th22 细胞在自身免疫性疾病发病机制中的作用
影响因子：
7.3
作者：
Jiang Q;Yang G;Xiao F;Xie J;Wang S;Lu L;Cui D
通讯作者：
Cui D
影响因子：
4.6
作者：
Hileman CO;Funderburg NT
通讯作者：
Funderburg NT
影响因子：
4.8
作者：
Diegmann, Julia;Junker, Kerstin;von Eggeling, Ferdinand
通讯作者：
von Eggeling, Ferdinand
影响因子：
30.5
作者：
Duhen, Thomas;Geiger, Rebekka;Sallusto, Federica
通讯作者：
Sallusto, Federica