Study on the role of plasmacytoid dendritic cells in human normal and inflammatory conditions

浆细胞样树突状细胞在人类正常和炎症条件下的作用研究

• 批准号: 14570145
• 负责人: TAKAHASHI Kiyoshi
• 金额: $ 1.73万
• 依托单位: OKAYAMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570145/
• 关键词: dendritic cells; plasmacytoid dendritic cells; interdigitating dendritic cells; cell origin; immunohistochemistry; human lymphoid tissues; plasmacytoid dendritic cell; interdigitating dendritic cell; immunofluorescent microscopy; human tonsil; d

In 2002, I_studied the distribution, morphology, and immunophenotype of PDC in the human tonsil by immunofluorescent microscopy using monoclonal antibody CD123. The results indicated that PDC, which were identified as CD123+ lymphoid cells, were distributed in the T-cell area of the tonsil, especially around high endothelial venules (HEV). They coexpressed CD4, CD40, CD45RA, CD68, but not IDC-markers including CD83 and CD86. They were accumulated and formed large homotipic aggregates around HEV. PDC tended to be distributed separately from IDC, which were extensively dendriform cells positive for HLA-DR, CD83 and CD86. There was no cells showing features intermediate between PDC and IDC. On the contrary, PDC differentiated into IDC when cultured in the presence of IL-3 and CD40-ligand. These findings suggest that in the tonsil PDC have their own role and their differentiation into IDC was inhibited. In 2003, I precisely studied immunophenotype of IDC using S100b protein and fascin, and … More found that IDC are phenotypically heterogenous. IDC were classified into three subsets, S100b+ fascin-IDC (IDC-1), S100b+ fascin+ IDC (IDC-2), and S100b-fascin+ IDC (IDC-3). IDC-3 were morphologically different from S100b+ IDC (IDC-1 and IDC-2). Namely, IDC-1 tended to be larger and more dendritic in shape. Moreover, IDC-3 were stable, while IDC-1 and IDC-2 were unstable and tended to undergo apoptosis when cultured in vitro. We also found that numerous IDC-3 were present, while S100b+ IDC were scarce in histiocytic necrotizing, lymphadenitis (Kikuchi's disease). Insead of S100b+ IDC, numerous S100b+ T-cells, which expressed CD3 and CD8, were present around IDC-3. In contrast, there were a small number of IDC-3 and S100b+ T-cells in nonspecific lymphadenitis, tuberculous lymphadenitis, and sarcoidosis. These findings suggest that the origin of IDC-3 is different from the origin of S 100b+ IDC (IDC-1 and IDC-2). It is suggested that IDC-3 are derived from S100b-negative progenitors, while S100b+ IDC are derived from S100b+ progenitors. When PDC were cultured in the presence of CD40L, they differentiated into mature DC positive for CD83 and CD86, but negative for S100b, suggesting that S100b-negative IDC (IDC-3) are derived from PDC, while S100b+ IDC are derived from Langerhans cells and S100b+ T-cells. Less

2002年，我用单抗CD123用免疫荧光显微镜研究了PDC在人扁桃体中的分布、形态和免疫表型。结果表明，PDC主要分布于扁桃体的T细胞区，尤其是高内皮微静脉周围，为CD123+淋巴样细胞。共表达CD_4、CD_(40)、CD_(45)RA、CD_(68)，但不表达包括CD_(83)、CD_(86)在内的IDC标志物。它们在HEV周围聚集并形成大的同质聚集体。PDC倾向于与IDC分开分布，IDC是广泛表达HLA-DR、CD83和CD86的树突状细胞。没有细胞显示介于PDC和IDC之间的特征。相反，在IL-3和CD40配体存在的情况下，PDC向IDC分化。这些发现提示PDC在扁桃体中有其自身的作用，其向IDC的分化受到抑制。2003年，我用S100B蛋白和Fasin，以及…，对IDC的免疫表型进行了精确的研究更多的人发现IDC具有表型异质性。IDC分为三个亚型，即S100B+Fascin-IDC(IDC-1)、S100B+Fascin+IDC(IDC-2)和S100B-Fascin+IDC(IDC-3)。IDC-3在形态上与S100B+IDC(IDC-1和IDC-2)不同。也就是说，IDC-1倾向于更大、更树枝状的形状。体外培养时，IDC-3细胞稳定，IDC-1和IDC-2细胞不稳定，易发生细胞凋亡。我们还发现，在组织细胞坏死性淋巴结炎(菊池病)中，IDC-3大量存在，而S100B+IDC很少。在S100B+IDC中，IDC-3周围可见大量表达CD3和CD8的S100B+T细胞。而在非特异性淋巴结炎、结核性淋巴结炎和结节病中仅有少量的IDC-3和S100B+T细胞。这些发现表明，IDC-3的起源与S 100b+IDC(IDC-1和IDC-2)的起源不同。提示IDC-3来源于S100B阴性祖细胞，而S100B+IDC来源于S100B+祖细胞。当PDC在CD40L存在下培养时，分化为CD83和CD86阳性而S100B阴性的成熟DC，提示S100B阴性的IDC(IDC-3)来自PDC，而S100B+IDC来自朗格汉斯细胞和S100B+T细胞。较少

项目成果

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