A Clonogenic Progenitor with Prominent Plasmacytoid Dendritic Cell Developmental Potential

A Clonogenic Progenitor with Prominent Plasmacytoid Dendritic Cell Developmental Potential
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DOI:
10.1016/j.immuni.2013.04.006
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发表时间:
2013-05-23
期刊:
影响因子:
32.4
通讯作者:
Ohteki, Toshiaki
Ohteki, Toshiaki
中科院分区:
医学1区
文献类型:
--
作者:
Onai, Nobuyuki;Kurabayashi, Kazutaka;Ohteki, Toshiaki

文献摘要

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巨噬细胞和树突状细胞(DC)祖细胞(MDPs)和普通DC祖细胞(CDPs)是具有DC分化潜力的骨髓(BM)祖细胞。然而,MDPs和CDPs都会产生大量的常规dc (cdc)和少量浆细胞样dc (pDCs),这意味着更多特异性的pDC祖细胞仍有待鉴定。在这里,我们描述了具有突出pDC分化潜力的DC祖细胞。虽然MDPs和CDPs都表达巨噬细胞集落刺激因子(M-CSF)受体(M-CSFR),但其祖细胞仅限于M-CSFR-部分,鉴定为Lin(-)c-Kit(int/lo)Flt3(+)M-CSFR-,并表达大量E2-2(也称为Tcf4),这是pDC发育的必要转录因子。重要的是,它们似乎直接来源于CDPs或淋巴细胞引发的多能祖细胞(lmpp)。总的来说,我们的研究结果提供了对DC分化途径的深入了解,并可能导致基于祖细胞的治疗应用于感染和自身免疫性疾病。
Macrophage and dendritic cell (DC) progenitors (MDPs) and common DC progenitors (CDPs) are bone marrow (BM) progenitors with DC differentiation potential. However, both MDPs and CDPs give rise to large numbers of conventional DCs (cDCs) and few plasmacytoid DCs (pDCs), implying that more dedicated pDC progenitors remain to be identified. Here we have described DC progenitors with a prominent pDC differentiation potential. Although both MDPs and CDPs express the macrophage colony stimulating factor (M-CSF) receptor (M-CSFR), the progenitors were confined to a M-CSFR- fraction, identified as Lin(-)c-Kit(int/lo)Flt3(+)M-CSFR-, and expressed high amounts of E2-2 (also known as Tcf4) an essential transcription factor for pDC development. Importantly, they appeared to be directly derived from either CDPs or lymphoid-primed multi-potent progenitors (LMPPs). Collectively, our findings provide insight into DC differentiation pathways and may lead to progenitor-based therapeutic applications for infection and autoimmune disease.