Osteopontin aggravates experimental autoimmune uveoretinitis in mice
Osteopontin aggravates experimental autoimmune uveoretinitis in mice
复制标题
DOI：
10.4049/jimmunol.178.10.6567
复制
发表时间：
2007-05-15
影响因子：
4.4
通讯作者：
Onoe, Kazunori
中科院分区：
文献类型：
--
作者：
Kitamura, Mizuki;Iwabuchi, Kazuya;Onoe, Kazunori
人类内源性葡萄膜炎是一种常见的威胁视力的眼内炎性疾病，已通过实验性自身免疫性葡萄膜视网膜炎(EAU)的小鼠模型进行了广泛的研究。它可能是由Th1免疫反应介导的。在本研究中，我们研究了骨桥蛋白(OPN)的作用，骨桥蛋白是一种具有多种功能的蛋白质，有助于Th1细胞介导的免疫的发展。随着EAU的进展，在用人视黄酸受体间结合蛋白(HIRBP)肽1-20免疫的野生型(WT)小鼠中，OPN升高。与WT小鼠相比，OPN缺陷(OPN-/-)小鼠在临床和组织病理学评分上表现出较轻的EAU进展。与WT T细胞相比，hIRBP免疫OPN-/-小鼠的T细胞具有较低的抗原特异性增殖和促炎细胞因子(肿瘤坏死因子-α和干扰素-γ)的产生。当给予hIRBP免疫的WT小鼠注射与OPN中的整合素的隐蔽结合位点SLAYGLR序列反应的M5抗体时，EAU的发育显著改善。经hIRBP免疫的WT小鼠T细胞在含有M5抗体的情况下，经hIRBP多肽刺激后，T细胞的增殖反应和促炎细胞因子的产生显著降低。我们目前的结果表明，OPN可能是控制葡萄膜视网膜炎的一个新的治疗靶点。免疫学杂志，2007,178：6567-6572。
Human endogenous uveitis is a common sight-threatening intraocular inflammatory disease and has been studied extensively using a murine model of experimental autoimmune uveoretinitis (EAU). It is possibly mediated by Th1 immune responses. In the present study, we investigated the role of osteopontin (OPN), a protein with pleiotropic functions that contributes to the development of Th1 cell-mediated immunity. Accompanying EAU progression, OPN was elevated in wild-type (WT) mice that had been immunized with human interphotoreceptor retinoid-binding protein (hIRBP) peptide 1-20. OPN-deficient (OPN-/-) mice showed milder EAU progression in clinical and histopathological scores compared with those of WT mice. The T cells from hIRBPimmunized OPN-/- mice exhibited reduced Ag-specific proliferation and proinflammatory cytokine (TNF-alpha and IFN-,gamma) production compared with those of WT T cells. When hIRBP-immunized WT mice were administered M5 Ab reacting to SLAYGLR sequence, a cryptic binding site to integrins within OPN, EAU development was significantly ameliorated. T cells from hIRBPimmunized WT mice showed significantly reduced proliferative responses and proinflammatory cytokine production upon stimulation with hIRBP peptide in the presence of M5 Ab in the culture. Our present results demonstrate that OPN may represent a novel therapeutic target to control uveoretinitis. The Journal of Immunology, 2007, 178: 6567-6572.