Yu Xijun, Fukunaga Atsushi, Nagai Hiroshi, Oniki Shuntaro, Honma Nakayuki, Ichihashi Masamitsu, Matozaki Takashi, Nishigori Chikako, Horikawa Tatsuya
Division of Dermatology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
J Invest Dermatol. 2006 Apr;126(4):797-807. doi: 10.1038/sj.jid.5700176.
CD47 is a membrane-associated glycoprotein that suppresses the function of immune cells. We previously reported that Langerhans cells (LCs) express Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1), a ligand for CD47, which plays an important role in the regulation of their motility. In this study, we show that LCs also express CD47, and that ligation of CD47 with SHPS-1-Fc fusion protein in vivo diminishes the development of the contact hypersensitivity response. We further demonstrate that CD47 engagement affects immune functions of LCs. CD47 engagement in vivo significantly inhibits the emigration of LCs from the epidermis into draining lymph nodes following treatment with haptens and tumor necrosis factor-alpha. The emigration of dendritic cells from skin explants into the medium and the chemotaxis of murine XS52 dendritic cells were significantly reduced by treatment with SHPS-1-Fc or an anti-CD47 mAb. Under explant culture system, SHPS-1-Fc treatment suppressed the expression of CD80 and CD86 of LCs. These effects on LCs and contact hypersensitivity response of CD47 ligation were reversed by treatment with pertussis toxin. These results suggest that the ligation of CD47 inhibits the migration of LCs and the expression of B7 costimulatory molecules, which results in inhibition of the contact hypersensitivity response.
CD47是一种膜相关糖蛋白，可抑制免疫细胞的功能。我们之前报道过，朗格汉斯细胞（LCs）表达含Src同源2结构域的蛋白酪氨酸磷酸酶底物1（SHPS-1），它是CD47的一种配体，在调节其运动性方面发挥重要作用。在本研究中，我们发现LCs也表达CD47，并且在体内用SHPS-1-Fc融合蛋白连接CD47会减少接触性超敏反应的发生。我们进一步证明，CD47的结合会影响LCs的免疫功能。在体内用半抗原和肿瘤坏死因子-α处理后，CD47的结合显著抑制LCs从表皮迁移至引流淋巴结。用SHPS-1-Fc或抗CD47单克隆抗体处理可显著降低皮肤外植体中树突状细胞向培养基中的迁移以及小鼠XS52树突状细胞的趋化性。在外植体培养系统中，SHPS-1-Fc处理可抑制LCs的CD80和CD86表达。用百日咳毒素处理可逆转CD47结合对LCs和接触性超敏反应的这些影响。这些结果表明，CD47的结合会抑制LCs的迁移和B7共刺激分子的表达，从而导致接触性超敏反应受到抑制。
