Langerhans cells (LC) are the prototype langerin-expressing dendritic cells (DC) that reside specifically in the epidermis, but langerin-expressing conventional DCs also reside in the dermis and other tissues, yet the factors that regulate their development are unclear. Because retinoic acid receptor alpha (RARα) is highly expressed by LCs, we investigate the functions of RARα and retinoic acid (RA) in regulating the langerin-expressing DCs. Here we show that the development of LCs from embryonic and bone marrow-derived progenitors and langerin⁺ conventional DCs is profoundly regulated by the RARα-RA axis. During LC differentiation, RARα is required for the expression of a LC-promoting transcription factor Runx3, but suppresses that of LC-inhibiting C/EBPβ. RARα promotes the development of LCs and langerin⁺ conventional DCs only in hypo-RA conditions, a function effectively suppressed at systemic RA levels. Our findings identify positive and negative regulatory mechanisms to tightly regulate the development of the specialized DC populations.

中文翻译：

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RARα支持朗格汉斯细胞和表达陈旧性树胶的常规树突状细胞的发育。

朗格汉斯细胞（LC）是专门表达在表皮中的表达陈皮素的树突状细胞（DC），但是表达陈皮素的常规DC也存在于真皮和其他组织中，但尚不清楚调节其发育的因素。由于视黄酸受体α（RARα）在LC中高度表达，因此我们研究了RARα和视黄酸（RA）在调节表达木质素的DC中的功能。在这里，我们显示了从胚胎和骨髓来源的祖细胞和langerin ⁺ 常规DC到LC的发育都受到RARα-RA轴的深刻调控。在LC分化过程中，RARα是表达LC促进转录因子Runx3所必需的，但会抑制LC抑制C /EBPβ的表达。RARα促进LC和Langerin的发展⁺仅在低RA条件下使用常规DC，该功能在全身RA水平上得到有效抑制。我们的发现确定了积极和消极的监管机制，以严格监管专业DC人群的发展。