Essential roles of SIRPα in homeostatic regulation of skin dendritic cells
Essential roles of SIRPα in homeostatic regulation of skin dendritic cells
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DOI：
10.1016/j.imlet.2010.10.004
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发表时间：
2011-03-30
影响因子：
4.4
通讯作者：
Matozaki, Takashi
中科院分区：
文献类型：
--
作者：
Iwamura, Hiroko;Saito, Yasuyuki;Matozaki, Takashi
信号调节蛋白α(SIRPα)是一种免疫球蛋白超家族蛋白，主要表达于树突状细胞(DC)。它的胞内区与SHP-1或SHP-2蛋白酪氨酸磷酸酶结合，胞外区与另一种免疫球蛋白超家族蛋白CD47相互作用，构成细胞-细胞信号。SIRPα以前被证明对接触性超敏反应的发展很重要，这可能是因为它对树突状细胞对CD4(+)T细胞的启动具有积极的调节作用。然而，SIRPα调节DC功能的机制仍不清楚。在这里，我们发现，与野生型(WT)小鼠相比，表达SIRPα突变形式的小鼠外周淋巴结(LNS)中的I-A(+)细胞数量显著减少，与野生型(WT)小鼠相比，I-A(+)细胞的数量显著减少。此外，用异硫氰酸荧光素(FITC)涂抹皮肤后，SIRPα突变小鼠引流淋巴结(LNS)中含异硫氰酸酯(FITC)的I-A(+)细胞的增加明显减弱。然而，从SIRPα突变小鼠制备的骨髓来源的DC的迁移能力以及CCR7的表达并未受到损害。与WT小鼠相比，SIRPα突变小鼠表皮中I-(+)A LC的数量明显减少。此外，SIRPα突变小鼠LCS中转化生长因子-β受体II的mRNA表达明显低于WT小鼠。这些结果表明，SIRPα对皮肤中的LCS和LNS中的迁移性DC的动态平衡很重要，但不太可能使这些细胞从皮肤迁移到引流中的LNS。(C)2010爱思唯尔B.V.保留所有权利。
Signal regulatory protein alpha (SIRP alpha) is an immunoglobulin superfamily protein that is predominantly expressed in dendritic cells (DCs). Its cytoplasmic region binds SHP-1 or SHP-2 protein tyrosine phosphatases, while its extracellular region interacts with CD47, another immunoglobulin superfamily protein, constituting cell-cell signaling. SIRP alpha was previously shown to be important for development of contact hypersensitivity, likely as a result of its positive regulation of the priming by DCs of CD4(+) T cells. However, the mechanism by which SIRP alpha regulates DC functions remains unknown. Here we found that the number of I-A(+) cells, which represent migratory DCs such as Langerhans cells (LCs) or dermal DCs from the skin, in the peripheral lymph nodes (LNs) was markedly decreased in mice expressing a mutant form of SIRP alpha that lacks the cytoplasmic region compared with that of wild-type (WT) mice. In addition, an increase of fluorescein isothiocyanate (FITC)-bearing I-A(+) cells in the draining lymph nodes (LNs) after skin-painting with FITC was markedly blunted in SIRP alpha mutant mice. However, migratory ability, as well as expression of CCR7, of bone marrow-derived DCs prepared from SIRP alpha mutant mice were not impaired. By contrast, the number of I-(+)A LCs in the epidermis of SIRP alpha mutant mice was markedly decreased compared with that of WT mice. In addition, the mRNA expression of transforming growth factor-beta receptor II in LCs of SIRP alpha mutant mice was markedly decreased compared with that of WT mice. These results suggest that SIRP alpha is important for homeostasis of LCs in the skin, as well as of migratory DCs in the LNs, but unlikely for migration of these cells from the skin to draining LNs. (C) 2010 Elsevier B.V. All rights reserved.