The signal transducers STAT5 and STAT3 control expression of Id2 and E2-2 during dendritic cell development
The signal transducers STAT5 and STAT3 control expression of Id2 and E2-2 during dendritic cell development
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DOI：
10.1182/blood-2012-07-441311
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发表时间：
2012-11-22
期刊：
影响因子：
20.3
通讯作者：
Watowich, Stephanie S.
中科院分区：
文献类型：
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作者：
Li, Haiyan S.;Yang, Cliff Y.;Watowich, Stephanie S.
细胞因子和转录因子在树突状细胞（DC）的发育中起关键作用，但有关这些信号之间调控相互作用的信息仍然有限。在此我们表明，细胞因子粒细胞 - 巨噬细胞集落刺激因子（GM - CSF）和Flt3配体（Flt3L）诱导转录介质Id2和E2 - 2，并通过信号转导及转录激活因子（STAT）依赖性途径控制DC谱系的多样化。我们发现，在稳态或对GM - CSF的应答中，STAT5是组织CD103⁺ DC产生和浆细胞样DC（pDC）抑制所必需的。STAT5刺激Id2的GM - CSF依赖性表达，Id2控制CD103⁺ DC的产生和对pDC的抑制。相比之下，pDC而非CD103⁺ DC依赖于STAT3。一致地，STAT3刺激pDC调节因子Tcf4（E2 - 2）的Flt3L应答性表达。这些数据表明，STAT通过控制参与谱系分化的转录因子促进DC的发育。（《血液》2012年；120(22):4363 - 4373）
Cytokines and transcription factors play key roles in dendritic cell (DC) development, yet information about regulatory interactions between these signals remains limited. Here we show that the cytokines GM-CSF and Flt3L induce the transcriptional mediators Id2 and E2-2 and control DC lineage diversification by STAT-dependent pathways. We found that STAT5 is required for tissue CD103(+) DC generation and plasmacytoid DC (pDC) suppression in steady state or response to GM-CSF. STAT5 stimulates GM-CSF-dependent expression of Id2, which controls CD103(+) DC production and pDC inhibition. By contrast, pDCs, but not CD103(+) DCs, are dependent on STAT3. Consistently, STAT3 stimulates Flt3L-responsive expression of the pDC regulator Tcf4 (E2-2). These data suggest that STATs contribute to DC development by controlling transcription factors involved in lineage differentiation. (Blood. 2012;120(22):4363-4373)