Mechanism of immune-surveillance and immune-regulation by paired receptors

由激活受体和抑制受体组成的成对受体似乎已经随着病原体如病毒而进化。然而，进一步的分析表明，一些配对受体识别特异性自身抗原。尤其是，主要在NK细胞和树突状细胞上表达的PILR识别在Th 2细胞上表达的特异性配体。本研究进一步筛选了PILR的配体，并分析了PILR在免疫监视中的作用。我们发现PILR的配体强烈激活NK细胞和树突细胞（Shiratori等人，J. Exp. Med.2004）。此外，我们发现在T细胞上表达的调节分子是PILR的配体（专利：PCT/JP 2007/053558）。此外，我们发现某些聚糖参与PILR的配体识别。为了分析PILR在体内的功能，我们成功地建立了PILR缺陷小鼠。PILR缺陷小鼠将提供更多的信息如何配对受体参与免疫监视。另一方面，我们发现抑制性CD 200受体在嗜碱性粒细胞上表达并调节嗜碱性粒细胞的活化（Shiratori et at J. Immunoi 2005）。由于嗜碱性粒细胞是已知的参与过敏反应，我们的研究提出了一个新的目标分子的调节过敏性疾病。

Paired receptors that consist of activating and inhibitory receptors seem to have been evolved with pathogens such as viruses. However, further analyses revealed that some of paired receptors recognize specific self-antigens. Especially, PILR that is mainly expressed on NK cells and dendritic cells recognizes specific ligand expressed on Th2 cells. In the present study, we further screened the ligand for PILR and analyzed the function of PILR in immune surveillance. We found that the ligand for PILR strongly activate NK cells and dendritic cells (Shiratori et aL J. Exp. Med. 2004). Furthermore, we found that regulatory molecules expressed on T cells are ligand for PILR (Patent : PCT/JP2007/053558). In addition, we found that certain glycan is involved in the ligand recognition by PILR. In order to analyze the function of PILR in vivo, we successfully established PILR-deficient mice. PILR-deficient mice will provide further information how paired receptors are involved in immune surveillance. On the other hand, we found that inhibitory CD200 receptor is expressed on basophil and regulates the activation of basophil (Shiratori et at J. Immunoi 2005). Because basophil is known to be involved in allergic response, our study suggested a new target molecule for the regulation of allergic diseases.