Wendland Meike, Czeloth Niklas, Mach Nicolas, Malissen Bernard, Kremmer Elisabeth, Pabst Oliver, Förster Reinhold
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6347-52. doi: 10.1073/pnas.0609180104. Epub 2007 Apr 2.
Small intestine plasmacytoid dendritic cells (pDC) are poorly characterized. Here, we demonstrate that intestinal pDC show the characteristic plasma cell-like morphology, and are recognized by antibodies against B220, Ly6c, 120G8, and PDCA-1, markers that are typically expressed by pDC. Furthermore, intestinal pDC carry high levels of CCR9 and are largely absent in the intestine, but not in lung, liver, or secondary lymphoid organs of CCR9-deficient animals. Competitive adoptive transfers reveal that CCR9-deficient pDC are impaired in homing to the small intestine after i.v. transfer. In a model of cholera toxin-induced gut inflammation, pDC are recruited to the intestine in WT but not CCR9-deficient animals. Furthermore, after oral application of a Toll-like receptor (TLR) 7/8 ligand, myeloid DC of the lamina propria are rapidly mobilized in WT but not in CCR9-deficient animals. Mobilization of myeloid DC can be completely rescued by adoptively transferred WT pDC to CCR9-deficient mice before oral challenge. Together, our data reveal an essential role for CCR9 in the homing of pDC to the intestine under homeostatic and inflammatory conditions and demonstrate an important role for intestinal pDC for the rapid mobilization of lamina propria DC.
小肠浆细胞样树突状细胞（pDC）的特征尚不明确。在此，我们证明肠道pDC呈现出典型的浆细胞样形态，并可被抗B220、Ly6c、120G8和PDCA-1抗体识别，这些标志物通常由pDC表达。此外，肠道pDC高水平表达CCR9，且在CCR9缺陷动物的肠道中大量缺失，但在肺、肝脏或次级淋巴器官中则不存在。竞争性过继转移显示，CCR9缺陷的pDC经静脉注射后归巢至小肠的能力受损。在霍乱毒素诱导的肠道炎症模型中，野生型动物的pDC被招募至肠道，而CCR9缺陷动物则不然。此外，口服Toll样受体（TLR）7/8配体后，野生型动物固有层的髓样DC迅速动员，而CCR9缺陷动物则无此现象。在口服攻击前，将野生型pDC过继转移至CCR9缺陷小鼠可完全挽救髓样DC的动员。总之，我们的数据揭示了CCR9在稳态和炎症条件下pDC归巢至肠道过程中的关键作用，并证明了肠道pDC在固有层DC快速动员中的重要作用。
