Differential involvement of PU.1 and Id2 downstream of TGF-β1 during Langerhans-cell commitment
Differential involvement of PU.1 and Id2 downstream of TGF-β1 during Langerhans-cell commitment
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DOI：
10.1182/blood-2005-04-1721
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发表时间：
2006-02-15
期刊：
影响因子：
20.3
通讯作者：
Strobl, H
中科院分区：
文献类型：
--
作者：
Heinz, LX;Platzer, B;Strobl, H
朗格汉斯细胞（Langerhans cells，LC）是表皮和粘膜组织中大量存在的树突状细胞（dendritic cells，DC）。转录因子PU.1和Id 2被认为是造血祖细胞LC发育的正调节因子。在体外和体内，从祖细胞分化为LC完全依赖于转化生长因子β 1 JGF-β 1;然而，下游机制定义不清。我们发现，在人CD 34（+）单核细胞/LC（M/LC）祖细胞中，PU.1和Id 2均由TGF-β 1诱导，并且无论是异位PU.1或Id 2单独还是两者一起，都不能取代TGF-β 1对LC定型的指导作用。然而，这两个因素通过作用于2个不同的交叉点而对LC分化做出了关键性贡献。异位PU.1强烈增强TGF-β 1依赖性LC的发展。此外，Notch诱导的树突状细胞的产生与PU.1上调有关。因此，PU.1通常在髓样DC发育期间增加。异位Id 2抑制在不存在TGF-β 1的情况下产生的细胞获得早期单核细胞特征，并且还抑制由替代刺激诱导的单核细胞。由于TGF-β 1抑制共同祖细胞的默认单核细胞途径，PU. 1和Id 2似乎调节TGF-β 1下游M/LC前体的谱系选择。
Langerhans cells (LCs) are highly abundant dendritic cells (DCs) in epidermal and mucosal tissues. The transcription factors PU.1 and Id2 have been implicated as positive regulators of LC development from hematopoietic progenitor cells. LC differentiation from progenitors is absolutely dependent on transforming growth factor beta 1 JGF-beta 1 in vitro as well as in vivo; however, downstream mechanisms are poorly defined. We found that both PU.1 and Id2 are induced by TGF-P1 in human CD34(+) monocyte/LC (M/LC) progenitor cells, and that neither ectopic PU.1 or Id2 alone, nor both together, could replace TGF-P1 in its instructive function on LC commitment. However, both factors critically contributed to LC differentiation by acting at 2 distinct intersection points. Ectopic PU.1 strongly enhanced TGF-beta 1-dependent LC development. Additionally, Notch-induced generation of interstitial-type DCs was associated with PU.1 up-regulation. Thus, PU.1 is generally increased during myeloid DC development. Ectopic Id2 inhibits the acquisition of early monocytic characteristics by cells generated in the absence of TGF-beta 1 and also inhibits monocyte induction by alternative stimuli. Since TGF-P1 represses a default monocyte pathway of common progenitor cells, PU.1 and Id2 seem to modulate lineage options of M/LC precursors, downstream of TGF-beta 1.