The two faces of IL-6 on Th1/Th2 differentiation
The two faces of IL-6 on Th1/Th2 differentiation
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DOI：
10.1016/s0161-5890(02)00210-9
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发表时间：
2002-12-01
影响因子：
3.6
通讯作者：
Rincón, M
中科院分区：
文献类型：
--
作者：
Diehl, S;Rincón, M
白介素6是一种由多种细胞产生的细胞因子，包括巨噬细胞、树突状细胞和B细胞等抗原提呈细胞。IL-6参与急性时相反应、B细胞成熟和巨噬细胞分化。在这里，我们讨论了IL-6的一项新功能：控制辅助性T细胞(Th)1/Th2分化。IL-6通过两个独立的分子机制促进Th2分化，同时抑制Th1极化。IL-6激活活化T细胞核因子(NFAT)介导的转录，导致初始的CD4(+)T细胞产生IL-4并分化为效应Th2细胞。IL-6诱导Th2分化依赖于内源性IL-4，而IL-6抑制Th1分化不依赖IL-4和NFAT。IL-6通过上调细胞因子信号转导抑制因子(SOCS)-1的表达，干扰IFNGamma信号转导和Th1细胞的发育，从而抑制Th1细胞的分化。由于IL-6是由APC大量产生的，因此它可能是CD4(+)T细胞活化过程中Th1/Th2早期调控的一个来源。因此，IL-6通过两种独立的分子机制在Th1/Th2分化中发挥双重作用。(C)2002爱思唯尔科学有限公司。保留所有权利。
Interleukin (IL)-6 is a cytokine produced by several cell types including antigen presenting cells (APC) such as macrophages, dendritic cells, and B cells. IL-6 is involved in the acute phase response, B cell maturation, and macrophage differentiation. Here, we discuss a novel function of IL-6: the control of T helper (Th) 1/Th2 differentiation. IL-6 promotes Th2 differentiation and simultaneously inhibits Th1 polarization through two independent molecular mechanisms. IL-6 activates transcription mediated by nuclear factor of activated T cells (NFAT) leading to production of IL-4 by naive CD4(+) T cells and their differentiation into effector Th2 cells. While the induction of Th2 differentiation by IL-6 is dependent upon endogenous IL-4, inhibition of Th1 differentiation by IL-6 is IL-4- and NFAT- independent. IL-6 inhibits Th1 differentiation by upregulating supressor of cytokine signaling (SOCS)-1 expression to interfere with IFNgamma signaling and the development of Th1 cells. Since IL-6 is abundantly produced by APC, it is a likely source of early Th1/Th2 control during CD4(+) T cell activation. Thus, by using two independent molecular mechanisms, IL-6 plays a dual role in Th1/Th2 differentiation. (C) 2002 Elsevier Science Ltd. All rights reserved.