Essential roles of SHPS-1 in induction of contact hypersensitivity of skin
Essential roles of SHPS-1 in induction of contact hypersensitivity of skin
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DOI：
10.1016/j.imlet.2008.08.005
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发表时间：
2008-11-16
影响因子：
4.4
通讯作者：
Matozaki, Takashi
中科院分区：
文献类型：
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作者：
Motegi, Sei-Ichiro;Okazawa, Hideki;Matozaki, Takashi
SHPS-I是一种跨膜蛋白，与蛋白酪氨酸磷酸酶SHP-1和SHP-2结合，在CD 11 c（+）树突状细胞（DC）表面大量存在。我们最近发现SHPS-1对于DC诱导CD 4（+）T细胞和Th 17细胞介导的实验性自身免疫的发展是必不可少的。我们现在进一步评估SHPS-1及其配体CD 47在2，4-二硝基氟苯（DNFB）接触性超敏反应（CHS）中的重要性。而DNFB诱导的CHS反应在表达缺少大部分胞质区域的SHPS-I突变形式的小鼠中受损，在CD 47缺陷小鼠中不受影响。此外，用阻断或不阻断SHPS-1与CD 47结合的SHPS-1单克隆抗体治疗野生型小鼠抑制了CHS反应。抗CD 47的mAb没有这种作用。2，4-二硝基苯磺酸诱导的DNFB致敏的野生型小鼠T细胞增殖和IFN-γ或IL-17的产生被SHPS-I的mAb抑制，但不被CD 47的mAb抑制。与此相反，SHPS-1的阻断mAb，而不是CD 47，抑制同种异体混合白细胞反应。抗SHPS-1的单克隆抗体，而不是抗CD 47的单克隆抗体，也抑制了脂多糖或聚肌胞苷酸诱导的DC产生TNF-α。这些结果表明SHPS-1在CHS的发生发展中是必不可少的，可能是由于其对DC对CD 4（+）T细胞的启动起正性调节作用。然而，SHPS-I的这种调节似乎不需要与CD 47相互作用。（C）2008 Elsevier B. V.保留所有权利。
SHPS-I is a transmembrane protein that binds the protein tyrosine phosphatases SHP-1 and SHP-2 and is abundant on the surface of CD11c(+) dendritic cells (DCs). We recently showed that SHPS-1 is essential for priming by DCs of CD4(+) T cells and for development of Th17 cell-mediated experimental autoimmunity. We have now further evaluated the importance of SHPS-1 and that of its ligand CD47 in contact hypersensitivity (CHS) to 2,4-dinitro-1-fluorobenzene (DNFB). Whereas the DNFB-induced CHS response was impaired in mice that express a Mutant form of SHPS-I lacking most of the cytoplasmic region, it was unaffected in CD47-deficient mice. Moreover, treatment of wild-type mice with mAbs to SHPS-1 that either block or do not block the binding of SHPS-1 to CD47 inhibited the CHS response. A mAb to CD47 had no such effect. The 2,4-dinitro-benzenesulfonic acid-induced proliferation of, and production of IFN-gamma or IL-17 by, T cells from DNFB-sensitized wild-type mice were inhibited by either mAb to SHPS-I but not by that to CD47. In contrast, the blocking mAbs to SHPS-1, but not that to CD47, inhibited an allogeneic mixed leukocyte reaction. Both mAbs to SHPS-1, but not that to CD47, also inhibited the lipopolysaccharide- or polyinosinic-polycytidylic acid-induced production of TNF-alpha by DCs. These results suggest that SHPS-1 is essential for development of CHS, likely as a result of its positive regulation of the priming by DCs of CD4(+) T cells. However, such regulation by SHPS-I does not appear to require its interaction with CD47. (C)2008 Elsevier B.V. All rights reserved.