B7-DC regulates asthmatic response by an IFN-gamma-dependent mechanism.
B7-DC regulates asthmatic response by an IFN-gamma-dependent mechanism.
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发表时间：
2004
影响因子：
4.4
通讯作者：
Koichiro Matsumoto;H. Inoue;T. Nakano;Miyuki Tsuda;Yuki Yoshiura;S. Fukuyama;Fumihiko Tsushima;T. Hoshino;H. Aizawa;H. Akiba;D. Pardoll;N. Hara;H. Yagita;M. Azuma;Y. Nakanishi
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文献类型：
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作者：
Koichiro Matsumoto;H. Inoue;T. Nakano;Miyuki Tsuda;Yuki Yoshiura;S. Fukuyama;Fumihiko Tsushima;T. Hoshino;H. Aizawa;H. Akiba;D. Pardoll;N. Hara;H. Yagita;M. Azuma;Y. Nakanishi
B7-H1(PD-L1)和B7-DC(PD-L2)是程序性死亡-1(PD-1)的配体，PD-1是CD28/CTLA-4家族的成员，与外周免疫耐受有关。我们研究了B7-H1和B7-DC在卵清蛋白诱导的小鼠过敏性哮喘模型中的作用。B7-H1在幼龄小鼠肺组织的树突状细胞、巨噬细胞、B细胞和T细胞上呈结构性表达，在过敏原攻击后其表达显著增加。相反，B7-DC在幼龄小鼠树突状细胞上几乎不表达，但在过敏原攻击后上调，尽管巨噬细胞上B7-DC表达上调幅度很小。在变应原攻击时使用抗B7-DC单抗，而不是在致敏时使用抗B7-DC单抗，可显著增加小鼠的呼吸道高反应性和嗜酸性粒细胞增多。这种治疗还导致IL-5和IL-13的产生增加，而肺和引流淋巴结细胞的干扰素-γ的产生减少。当用抗干扰素-伽马单抗去除小鼠体内的干扰素-γ时，上述变化就会减弱。有趣的是，用抗B7-H1或抗PD-1单抗治疗对哮喘反应没有显著影响。这些结果表明，B7-DC通过一种依赖于干扰素-γ，但不依赖于PD-1的机制，在调节哮喘反应中发挥独特的作用。
B7-H1 (PD-L1) and B7-DC (PD-L2) are the ligands for programmed death-1 (PD-1), which is a member of the CD28/CTLA-4 family and has been implicated in peripheral tolerance. We investigated the roles of B7-H1 and B7-DC in a murine OVA-induced allergic asthma model. B7-H1 was constitutively expressed on dendritic cells, macrophages, B cells, and T cells in the lungs of naive mice, and its expression could be dramatically increased after allergen challenge. In contrast, B7-DC expression was scarcely expressed on dendritic cells in naive mice, but was up-regulated after allergen challenge, although the up-regulation of B7-DC expression on macrophages was minimal. Treatment of mice with anti-B7-DC mAb at the time of allergen challenge, but not at the time of sensitization, significantly increased their airway hyper-reactivity and eosinophilia. Such treatment also resulted in the increased production of IL-5 and IL-13, and decreased IFN-gamma production in the lungs and draining lymph node cells. These changes were diminished when mice were depleted of IFN-gamma by anti-IFN-gamma mAb pretreatment. Interestingly, treatment with anti-B7-H1 or anti-PD-1 mAb did not significantly affect the asthmatic response. These results suggest a unique role for B7-DC in the regulation of asthmatic response through an IFN-gamma-dependent, but PD-1-independent, mechanism.