Diehl Sean, Rincón Mercedes
Immunobiology Program, Department of Medicine, University of Vermont, Given Medical Building D305, Burlington, VT 05405, USA.
Mol Immunol. 2002 Dec;39(9):531-6. doi: 10.1016/s0161-5890(02)00210-9.
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 nai;ve 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.
白细胞介素（IL）-6是一种由多种细胞类型产生的细胞因子，包括抗原呈递细胞（APC），如巨噬细胞、树突状细胞和B细胞。IL-6参与急性期反应、B细胞成熟和巨噬细胞分化。在此，我们讨论IL-6的一种新功能：控制辅助性T（Th）1/Th2分化。IL-6通过两种独立的分子机制促进Th2分化，同时抑制Th1极化。IL-6激活由活化T细胞核因子（NFAT）介导的转录，导致幼稚CD4(+)T细胞产生IL-4并分化为效应性Th2细胞。虽然IL-6诱导Th2分化依赖于内源性IL-4，但IL-6抑制Th1分化不依赖于IL-4和NFAT。IL-6通过上调细胞因子信号转导抑制因子（SOCS）-1的表达来干扰IFNγ信号传导和Th1细胞的发育，从而抑制Th1分化。由于APC大量产生IL-6，它可能是CD4(+)T细胞活化过程中早期Th1/Th2控制的来源。因此，通过两种独立的分子机制，IL-6在Th1/Th2分化中发挥双重作用。
