Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032.
J Exp Med. 2013 Oct 21;210(11):2151-9. doi: 10.1084/jem.20130443. Epub 2013 Oct 7.
Plasmacytoid dendritic cells (pDCs) rapidly produce type I interferon (IFN-I) in response to viruses and are essential for antiviral immune responses. Although related to classical DCs (cDCs) in their development and expression profile, pDCs possess many distinct features. Unlike cDCs, pDCs develop in the bone marrow (BM) and emerge into peripheral lymphoid organs and tissues as fully differentiated cells. We now report that pDCs specifically express Runx2, a Runt family transcription factor that is essential for bone development. pDCs in Runx2-deficient mice developed normally in the BM but were greatly reduced in the periphery. The defect was cell-intrinsic and was associated with the retention of mature Ly49Q(+) pDCs in the BM. Runx2 was required for the expression of several pDC-enriched genes, including the chemokine receptors Ccr2 and Ccr5. Mature pDCs expressed high levels of Ccr5 at the cell surface, and Ccr5-deficient pDCs in a competitive setting were reduced in the periphery relative to the BM. Thus, Runx2 is required for the emergence of mature BM pDCs into the periphery, in a process that is partially dependent on Ccr5. These results establish Runx2 as a lineage-specific regulator of immune system development.
浆细胞样树突状细胞（pDCs）能迅速对病毒产生 I 型干扰素（IFN-I），是抗病毒免疫反应所必需的。尽管它们在发育和表达谱上与经典树突状细胞（cDCs）有关，但 pDCs 具有许多独特的特征。与 cDCs 不同，pDCs 在骨髓（BM）中发育，并作为完全分化的细胞出现在外周淋巴器官和组织中。我们现在报告 pDCs 特异性表达 Runx2，这是一种对于骨骼发育至关重要的 Runt 家族转录因子。Runx2 缺陷型小鼠中的 pDCs 在 BM 中正常发育，但在外周组织中显著减少。该缺陷是细胞内在的，与成熟 Ly49Q(+) pDCs 在 BM 中的滞留有关。Runx2 是几个 pDC 丰富基因的表达所必需的，包括趋化因子受体 Ccr2 和 Ccr5。成熟的 pDCs 在细胞表面表达高水平的 Ccr5，在竞争环境下 Ccr5 缺陷型 pDCs 在相对于 BM 的外周组织中减少。因此，Runx2 是成熟 BM pDCs 进入外周组织的出现所必需的，这个过程部分依赖于 Ccr5。这些结果确立了 Runx2 作为免疫系统发育的谱系特异性调节因子。
