B7-H3 Promotes Pathogenesis of Autoimmune Disease and Inflammation by Regulating the Activity of Different T Cell Subsets.
B7-H3 Promotes Pathogenesis of Autoimmune Disease and Inflammation by Regulating the Activity of Different T Cell Subsets.
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DOI：
10.1371/journal.pone.0130126
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Luo L;Zhu G;Xu H;Yao S;Zhou G;Zhu Y;Tamada K;Huang L;Flies AD;Broadwater M;Ruff W;van Deursen JM;Melero I;Zhu Z;Chen L
B7-H3是免疫球蛋白超家族中的细胞表面分子，在宿主T细胞免疫应答过程中，对自身抗原和病原体的反应经常上调。然而，B7-H3在T细胞亚群的差异调节中的作用在很大程度上仍然未知。因此，我们构建了一个新的B7-H3缺陷小鼠品系（B7-H3 KO），并评估了B7-H3在实验性自身免疫性脑脊髓炎（EAE）、实验性哮喘和胶原诱导关节炎（CIA）中调节Th1、Th2和Th17亚群的功能；这些小鼠模型分别用于预测多发性硬化症、哮喘和类风湿关节炎的人类免疫反应。在这里，我们证明了B7-H3 KO小鼠在EAE和CIA小鼠模型中与同窝小鼠相比，炎症明显减少，发病机制降低，疾病进展有限；这些结果伴随着IFN-γ和IL-17产生的减少。与此形成鲜明对比的是，B7-H3 KO小鼠出现了严重的卵清蛋白（OVA）诱导的哮喘，肺部嗜酸性粒细胞浸润，灌洗液中IL-5和IL-13升高，血液中IgE抗OVA抗体升高。我们的研究结果表明B7-H3对Th1/Th17具有共刺激功能，但对Th2反应具有共抑制功能。我们的研究表明B7-H3可以影响不同的T细胞亚群，这对调节人类自身免疫性疾病的发病机制和疾病进展具有重要意义。
B7-H3 is a cell surface molecule in the immunoglobulin superfamily that is frequently upregulated in response to autoantigens and pathogens during host T cell immune responses. However, B7-H3's role in the differential regulation of T cell subsets remains largely unknown. Therefore, we constructed a new B7-H3 deficient mouse strain (B7-H3 KO) and evaluated the functions of B7-H3 in the regulation of Th1, Th2, and Th17 subsets in experimental autoimmune encephalomyelitis (EAE), experimental asthma, and collagen-induced arthritis (CIA); these mouse models were used to predict human immune responses in multiple sclerosis, asthma, and rheumatoid arthritis, respectively. Here, we demonstrate that B7-H3 KO mice have significantly less inflammation, decreased pathogenesis, and limited disease progression in both EAE and CIA mouse models when compared with littermates; these results were accompanied by a decrease in IFN-γ and IL-17 production. In sharp contrast, B7-H3 KO mice developed severe ovalbumin (OVA)-induced asthma with characteristic infiltrations of eosinophils in the lung, increased IL-5 and IL-13 in lavage fluid, and elevated IgE anti-OVA antibodies in the blood. Our results suggest B7-H3 has a costimulatory function on Th1/Th17 but a coinhibitory function on Th2 responses. Our studies reveal that B7-H3 could affect different T cell subsets which have important implications for regulating pathogenesis and disease progression in human autoimmune disease.
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T细胞共刺激和共抑制的分子机制。
DOI：
10.1038/nri3405
发表时间：
2013-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
30.5
作者：
Yamane H;Paul WE
通讯作者：
Paul WE
影响因子：
4.4
作者：
Luo, LQ;Chapoval, AI;Chen, LP
通讯作者：
Chen, LP
DOI：
10.1073/pnas.0405259101
发表时间：
2004-08-31
影响因子：
11.1
作者：
Suh, WK;Wang, SX;Mak, TW
通讯作者：
Mak, TW
影响因子：
4.4
作者：
Prasad, DVR;Nguyen, T;Dong, C
通讯作者：
Dong, C