TNF-alpha: an activator of CD4+FoxP3+TNFR2+ regulatory T cells.
TNF-alpha: an activator of CD4+FoxP3+TNFR2+ regulatory T cells.
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DOI：
10.1159/000289201
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Oppenheim JJ
中科院分区：
文献类型：
--
作者：
Chen X;Oppenheim JJ
肿瘤坏死因子-α是一种多效性细胞因子，根据环境、暴露时间和疾病状态的不同，可具有促炎或免疫抑制作用。肿瘤坏死因子的相反作用的基础仍然难以捉摸。CD4+FoxP3+调节性T细胞(Tregs)占外周血中约10%的CD4细胞，作为免疫应答的关键调节细胞，其作用日益受到重视，这为我们提供了一个新的框架来定义肿瘤坏死因子的细胞和分子基础。肿瘤坏死因子本身可以克服T细胞受体刺激的树突状细胞的严重无能状态。此外，在与IL-2协同作用下，肿瘤坏死因子选择性地激活Tregs，导致细胞增殖，上调FoxP3的表达，增强其抑制活性。人和小鼠的Tregs都主要表达TNFR2，使肿瘤坏死因子能够增强Treg的活性，从而有助于限制过度免疫反应引起的附带损害，最终终止免疫反应。表达TNFR2的CD4+FoxP3+Tregs约占正常小鼠外周血Tregs的40%，是Tregs中抑制作用最强的亚群。本文将对肿瘤坏死因子在Treg功能中作用的研究进行综述。此外，还将考虑Tregs在自身免疫性疾病和癌症中的作用，以及抗肿瘤坏死因子治疗对Tregs的影响，特别是在类风湿性关节炎中的作用。
TNF-α (TNF) is a pleiotropic cytokine which can have proinflammatory or immunosuppressive effects, depending on the context, duration of exposure and disease state. The basis for the opposing actions of TNF remains elusive. The growing appreciation of CD4+FoxP3+ regulatory T cells (Tregs), which comprise ~10% of peripheral CD4 cells, as pivotal regulators of immune responses has provided a new framework to define the cellular and molecular basis underlying the contrasting action of TNF. TNF by itself can overcome the profound anergic state of T cell receptor-stimulated Tregs. Furthermore, in concert with IL-2, TNF selectively activates Tregs, resulting in proliferation, upregulation of FoxP3 expression and increases in their suppressive activity. Both human and mouse Tregs predominantly express TNFR2, making it possible for TNF to enhance Treg activity, which helps limit the collateral damage caused by excessive immune responses and eventually terminates immune response. TNFR2-expressing CD4+FoxP3+ Tregs comprise ~40% of peripheral Tregs in normal mice and present the maximally suppressive subset of Tregs. In this review, studies describing the action of TNF on Treg function will be discussed. The role of Tregs in the autoimmune disorders and cancer as well as the effect of anti-TNF therapy on Tregs, especially in rheumatoid arthritis, will also be considered.
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DOI：
10.1084/jem.185.9.1573
发表时间：
1997-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cope AP;Liblau RS;Yang XD;Congia M;Laudanna C;Schreiber RD;Probert L;Kollias G;McDevitt HO
通讯作者：
McDevitt HO
影响因子：
27.4
作者：
Clark, J;Vagenas, P;Cope, AP
通讯作者：
Cope, AP
影响因子：
3.1
作者：
Ebach, DR;Riehl, TE;Stenson, WF
通讯作者：
Stenson, WF
影响因子：
6.4
作者：
Ausiello, CM;Fedele, G;Cassone, A
通讯作者：
Cassone, A
影响因子：
4.4
作者：
Deepe, George S., Jr.;Gibbons, Reta S.
通讯作者：
Gibbons, Reta S.