Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells.
Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells.
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DOI：
10.1084/jem.185.5.817
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发表时间：
1997-03-03
影响因子：
15.3
通讯作者：
Murphy, KM
中科院分区：
文献类型：
--
作者：
Szabo, SJ;Dighe, AS;Gubler, U;Murphy, KM
对T辅助细胞1(Th1)或Th2型反应的发育承诺可以显著影响宿主对病原体的免疫。在Th2发育的早期，IL-12信号通路的消失提供了一种允许稳定表型承诺的机制。在这篇报道中，我们证明了早期Th2细胞中IL-12信号的消失是由于IL-12受体(IL-12R)β2亚单位表达的选择性丧失。为了确定这种选择性缺失的基础，我们检测了IL-12Rβ2亚单位在Th细胞发育过程中对不同细胞因子处理的T细胞的反应。IL-12Rβ-2不是由幼稚的静息T细胞表达的，而是通过T细胞受体在抗原激活时被诱导。重要的是，IL-4和干扰素-γ可显著改变T细胞活化后IL-12受体β-2的表达。IL-4抑制IL-12Rβ2的表达，导致IL-12信号的丢失，为促进对Th2途径的承诺提供了一个重要的调节点。干扰素-γ治疗早期发育的Th2细胞维持了IL-12Rβ2的表达，并恢复了这些细胞对IL-12的功能反应能力，但不直接抑制IL-4或诱导干扰素-γ的产生。因此，干扰素-γ可能会阻止早期Th细胞过早进入Th2途径。控制IL-12Rβ2亚单位的表达可能是重定向正在进行的Th细胞应答的重要治疗靶点。
The developmental commitment to a T helper 1 (Th1)- or Th2-type response can significantly influence host immunity to pathogens. Extinction of the IL-12 signaling pathway during early Th2 development provides a mechanism that allows stable phenotype commitment. In this report we demonstrate that extinction of IL-12 signaling in early Th2 cells results from a selective loss of IL-12 receptor (IL-12R) β2 subunit expression. To determine the basis for this selective loss, we examined IL-12R β2 subunit expression during Th cell development in response to T cell treatment with different cytokines. IL-12R β2 is not expressed by naive resting CD4+ T cells, but is induced upon antigen activation through the T cell receptor. Importantly, IL-4 and IFN-γ were found to significantly modify IL-12 receptor β2 expression after T cell activation. IL-4 inhibited IL-12R β2 expression leading to the loss of IL-12 signaling, providing an important point of regulation to promote commitment to the Th2 pathway. IFN-γ treatment of early developing Th2 cells maintained IL-12R β2 expression and restored the ability of these cells to functionally respond to IL-12, but did not directly inhibit IL-4 or induce IFN-γ production. Thus, IFN-γ may prevent early Th cells from premature commitment to the Th2 pathway. Controlling the expression of the IL-12R β2 subunit could be an important therapeutic target for the redirection of ongoing Th cell responses.
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DOI：
10.1084/jem.177.4.1199
发表时间：
1993-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Manetti R;Parronchi P;Giudizi MG;Piccinni MP;Maggi E;Trinchieri G;Romagnani S
通讯作者：
Romagnani S
DOI：
10.1084/jem.179.4.1273
发表时间：
1994-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Manetti R;Gerosa F;Giudizi MG;Biagiotti R;Parronchi P;Piccinni MP;Sampognaro S;Maggi E;Romagnani S;Trinchieri G
通讯作者：
Trinchieri G
影响因子：
64.8
作者：
OHARA, J;PAUL, WE
通讯作者：
PAUL, WE
影响因子：
56.9
作者：
Guler, ML;Gorham, JD;Murphy, KM
通讯作者：
Murphy, KM
DOI：
10.1084/jem.181.5.1755
发表时间：
1995-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jacobson NG;Szabo SJ;Weber-Nordt RM;Zhong Z;Schreiber RD;Darnell JE Jr;Murphy KM
通讯作者：
Murphy KM