Interleukin-2 receptor downstream events in regulatory T cells - Implications for the choice of immunosuppressive drug therapy
Interleukin-2 receptor downstream events in regulatory T cells - Implications for the choice of immunosuppressive drug therapy
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DOI：
10.4161/cc.7.4.5454
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发表时间：
2008-02-15
期刊：
影响因子：
4.3
通讯作者：
Negrin, Robert S.
中科院分区：
文献类型：
--
作者：
Zeiser, Robert;Negrin, Robert S.
天然存在的CD 4（+）CD 25（高）FOXP 3（+）调节性T细胞（TCRs）构成了免疫调节的强大机制，因此，对诸如自身免疫性疾病、同种异体移植物排斥和移植物抗宿主病的疾病具有重要的治疗潜力。白细胞介素（IL）-2基因或IL-2受体（R）复合物组分的遗传缺陷对IL-2 R信号传导途径的破坏导致严重的T细胞介导的自身免疫，而不是免疫缺陷，表明IL-2 R信号传导对Treg发育和功能的关键作用。IL-2 R下游的信号传导可通过磷脂酰肌醇3-激酶（PI 3 K）/Akt/mTOR途径、Janus激酶（JAK）/信号转导和转录激活因子（STAT）途径和促分裂原活化蛋白激酶（MAPK）途径起作用。在这份报告中，我们专注于这些途径的相关性，以及免疫抑制药物的影响，可能会影响或增强调节性T细胞功能，通过靶向IL-2 R信号转导。
Naturally occurring CD4(+)CD25(high)FOXP3(+) regulatory T cells (Tregs) constitute a powerful mechanism of immune regulation and therefore, have important therapeutic potential for disorders such as autoimmune diseases, allograft rejection and graft-versus-host disease. Disruption of the IL-2R signalling pathway by genetic defects of the interleukin (IL)-2 gene or components of the IL-2 receptor (R) complex results in severe T cell-mediated autoimmunity rather than immunodeficiency, indicating a crucial role for IL-2R signalling for Treg development and function. Signalling downstream of the IL-2R can act through the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway, the Janus kinase (JAK)/Signal transducers and Activators of Transcription (STAT) pathway and the mitogen-activated protein kinase (MAPK) pathway. In this report we focus on the relevance of these pathways as well as the impact of immunosuppressive drugs that may affect or enhance Treg function by targeting IL-2R signalling.