Role of cytokines in thymus- versus peripherally derived-regulatory T cell differentiation and function.
Role of cytokines in thymus- versus peripherally derived-regulatory T cell differentiation and function.
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DOI：
10.3389/fimmu.2013.00155
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发表时间：
2013
影响因子：
7.3
通讯作者：
Piaggio E
中科院分区：
文献类型：
--
作者：
Goldstein JD;Pérol L;Zaragoza B;Baeyens A;Marodon G;Piaggio E
CD 4 + CD 25 + Foxp 3+调节性T细胞（TCRs）是控制免疫应答的重要参与者。最近，根据它们的起源，已经描述了两个主要的Tcls亚类：胸腺衍生的Tcls（tTcls）和外周衍生的Tcls（pTcls）。包括IL-2/STAT 5或TGF-β/Smad 3通路在内的许多信号通路在分离这两种谱系中起着至关重要的作用。在这里，我们回顾了IL-2，TGF-β和TNF-α三种主要细胞因子参与tTreg和pTreg生成，稳态和功能的不同需求的一些信息。如今，很明显，通过IL-2和IL-15共有的IL-2 R β链（CD 122）的信号传导对于tTreg的适当分化以及外周中的tTreg和pTreg存活是必需的。这一概念导致了基于低剂量IL-2给药的有前景的治疗策略的发展，以促进患者自身的Treg区室并抑制自身免疫和炎症。此外，确凿的证据表明TGF-β是pTreg分化和稳态的主要调节剂。然而，由于毒性和安全性问题，TGF-β的治疗性施用难以实施。关于TNF-α在TcB生物学中的作用的知识在小鼠和人类之间是不完整和不一致的。此外，临床使用TNF-α抑制剂的新结果表明，其抗炎作用的一部分可能取决于其对TNF的作用。考虑到大量的临床试验测试细胞因子施用或阻断以调节炎性疾病，更好地了解细胞因子对tT细胞和pT细胞生物学的影响对于提高这些免疫疗法的效率是必要的。
CD4+CD25+Foxp3+ regulatory T cells (Tregs) are essential players in the control of immune responses. Recently, accordingly to their origin, two main subsets of Tregs have been described: thymus-derived Tregs (tTregs) and peripherally derived Tregs (pTregs). Numerous signaling pathways including the IL-2/STAT5 or the TGF-β/Smad3 pathways play a crucial role in segregating the two lineages. Here, we review some of the information existing on the distinct requirements of IL-2, TGF-β, and TNF-α three major cytokines involved in tTreg and pTreg generation, homeostasis and function. Today it is clear that signaling via the IL-2Rβ chain (CD122) common to IL-2 and IL-15 is required for proper differentiation of tTregs and for tTreg and pTreg survival in the periphery. This notion has led to the development of promising therapeutic strategies based on low-dose IL-2 administration to boost the patients’ own Treg compartment and dampen autoimmunity and inflammation. Also, solid evidence points to TGF-β as the master regulator of pTreg differentiation and homeostasis. However, therapeutic administration of TGF-β is difficult to implement due to toxicity and safety issues. Knowledge on the role of TNF-α on the biology of Tregs is fragmentary and inconsistent between mice and humans. Moreover, emerging results from the clinical use of TNF-α inhibitors indicate that part of their anti-inflammatory effect may be dependent on their action on Tregs. Given the profusion of clinical trials testing cytokine administration or blocking to modulate inflammatory diseases, a better knowledge of the effects of cytokines on tTregs and pTregs biology is necessary to improve the efficiency of these immunotherapies.
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影响因子：
4.4
作者：
Burchill, Matthew A.;Yang, Jianying;Farrar, Michael A.
通讯作者：
Farrar, Michael A.
影响因子：
15.3
作者：
Fahlén, L;Read, S;Gorelik, L;Hurst, SD;Coffman, RL;Flavell, RA;Powrie, F
通讯作者：
Powrie, F
DOI：
10.1159/000289201
发表时间：
2010
期刊：
Current directions in autoimmunity
影响因子：
--
作者：
Chen X;Oppenheim JJ
通讯作者：
Oppenheim JJ
调节性T细胞在类风湿关节炎和抗TNFALPHA治疗中的逆转功能受损。
影响因子：
15.3
作者：
Ehrenstein, MR;Evans, JG;Singh, A;Moore, S;Warnes, G;Isenberg, DA;Mauri, C
通讯作者：
Mauri, C
影响因子：
4.4
作者：
Deepe, George S., Jr.;Gibbons, Reta S.
通讯作者：
Gibbons, Reta S.