Cross-regulation of signaling pathways by interferon-gamma: implications for immune responses and autoimmune diseases.

Cross-regulation of signaling pathways by interferon-gamma: implications for immune responses and autoimmune diseases.
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DOI:
10.1016/j.immuni.2009.09.002
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发表时间:
2009-10-16
期刊:
影响因子:
32.4
通讯作者:
Ivashkiv LB
Ivashkiv LB
中科院分区:
医学1区
文献类型:
--
作者:
Hu X;Ivashkiv LB

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IFN-γ是免疫和炎症的重要介质,其利用Jak-STAT途径激活STAT 1。IFN-γ的许多功能都归因于STAT 1介导的免疫效应基因的直接诱导,但最近人们发现,IFN-γ的关键功能是由细胞对其他细胞因子和炎症因子的反应的交叉调节介导的。本文综述了IFN-γ和STAT 1通过TLR、炎症因子、组织破坏性细胞因子、抗炎细胞因子和激活相反STATs的细胞因子调节信号传导的机制。这些信号传导机制揭示了IFN-γ如何调节巨噬细胞活化、炎症、组织重塑和Th和Treg分化,以及Th 1和Th 17应答如何整合在自身免疫性疾病中。
IFN-γ is an important mediator of immunity and inflammation that utilizes the Jak-STAT pathway to activate STAT1. Many functions of IFN-γ have been ascribed to direct STAT1-mediated induction of immune effector genes, but recently it has become clear that key IFN-γ functions are mediated by crossregulation of cellular responses to other cytokines and inflammatory factors. Here we review mechanisms by which IFN-γ and STAT1 regulate signaling by TLRs, inflammatory factors, tissue destructive cytokines, anti-inflammatory cytokines, and cytokines that activate opposing STATs. These signaling mechanisms reveal insights about how IFN-γ regulates macrophage activation, inflammation, tissue remodeling, and Th and Treg differentiation, and how Th1 and Th17 responses are integrated in autoimmune diseases.
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