最近，美国科学家发现了Th1分化的早期机制。目前，已发现三种类型的CD4 T辅助性细胞，它们分别是Th1、Th2和Th17。对于Th1而言，其最主要的特征是分泌大量的IFN-γ，并且受转录因子T-bet调控。此次研究发现，Jak3信号通路依赖性的染色体重建为T-bet调控Ifng基因的表达开启绿灯。Berg等人发现，在促进Th1分化的条件下，不表达Jak3（或者药物抑制Jak3的表达）的T细胞中IFN-γ的表达量急剧减少。然而，IFN-γ表达量的大幅度下降，既不是由于缺少TCR信号，也不是由于STAT1、STAT4或者T-bet的下调所引起。应用染色体免疫共沉淀发现，由于T-bet不能结合到Ifng基因近端的启动子上，从而使得这种细胞无法表达IFN-γ。此外，Ifng基因启动子区域组氨酸H3的乙酰化程度明显降低。为了进一步证实是何种细胞因子以及转录因子在Jak3信号通路中起作用，研究人员还发现STAT5能够与Ifng基因近端的启动子及其增强子CNS1结合。相反，使STAT5不表达或者阻断IL-2信号通路都能明显下调Th1分化过程中IFN-γ的表达。
那么，为什么T-bet对Ifng基因的“开与关”需要依赖于Jak3信号通路呢？其免疫学意义又是什么呢？还有待进一步研究。相关论文发表在《免疫》（Immunity）杂志上。（生物谷bioon.com）
生物谷推荐原始出处：
Immunity，Vol 28, 763-773，Min Shi，Leslie J. Berg
Janus-Kinase-3-Dependent Signals Induce Chromatin Remodeling at the Ifng Locus during T Helper 1 Cell Differentiation
Min Shi,1 Tsung H. Lin,2 Kenneth C. Appell,2 and Leslie J. Berg1,
1 Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
2 Pharmacopeia, PO Box 5350, Princeton, NJ 08540, USA
Corresponding author
Leslie J. Berg
leslie.berg@umassmed.edu
Summary
Differentiation of naive CD4+ T cells into T helper type 1 (Th1) effector cells requires both T cell receptor (TCR) signaling and cytokines such as interleukin-12 and interferon γ (IFN-γ). Here, we report that a third cytokine signal, mediated by the Janus family tyrosine kinase 3 (Jak3) and signal transducer and activator of transcription 5 (STAT5) pathway, is also required for Th1 cell differentiation. In the absence of Jak3-dependent signals, naive CD4+ T cells proliferate robustly but produce little IFN-γ after Th1 cell polarization in vitro. This defect is not due to reduced activation of STAT1 or STAT4 or to impaired upregulation of the transcription factor T-bet. Instead, we find that T-bet binding to the Ifng promoter is greatly diminished in the absence of Jak3-dependent signals, correlating with a decrease in Ifng promoter accessibility and histone acetylation. These data indicate that Jak3 regulates epigenetic modification and chromatin remodeling of the Ifng locus during Th1 cell differentiation.
