ICOS ligand expression is essential for allergic airway hyperresponsiveness
ICOS ligand expression is essential for allergic airway hyperresponsiveness
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DOI：
10.1093/intimm/dxq476
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发表时间：
2011-04-01
影响因子：
4.4
通讯作者：
Yang, Xi
中科院分区：
文献类型：
--
作者：
Kadkhoda, Kamran;Wang, Shuhe;Yang, Xi
诱导型共刺激分子配体（Inducible co-stimulator ligand，ICOSL）是一种新近定义的共刺激分子，它通过与T细胞表面表达的ICOS相互作用，在T细胞的活化、分化和功能中发挥重要作用。T（h）2型免疫应答对于包括哮喘在内的过敏性应答的发展和维持至关重要。使用基因敲除（KO）小鼠，我们已经评估了ICOSL在过敏性气道炎症和反应性中的作用，使用标准的小鼠哮喘模型由卵清蛋白（OVA）致敏和激发。我们的数据表明，OVA治疗的ICOSL KO小鼠表现出显着减少肺嗜酸性粒细胞浸润，组织病理学，粘液产生和几乎没有气道高反应性相比，野生型（Wt）的同行。血清抗体分析表明，抗原特异性IgG 1，IgG 2a和IgE滴度在ICOSL KO小鼠显着低于Wt对照组。此外，从ICOSL KO小鼠分离的CD 4（+）T细胞产生的T（h）2细胞因子（IL-4、IL-5、IL-10和IL-13）较少，但T（h）1（IFN-γ）和IL-17多于其Wt对照。综上所述，我们得出结论，ICOSL通过增强IgE抗体类别转换和T（h）2细胞因子的产生，减少T（h）17反应和气道嗜酸性粒细胞增多，在诱发个体过敏性气道高反应性中起重要作用。
Inducible co-stimulator ligand (ICOSL) is a rather newly defined co-stimulatory molecule, which, through interaction with ICOS expressed on T cells, plays an important role in T-cell activation, differentiation and function. T(h)2-type immune responses are critical for the development and maintenance of allergic responses including asthma. Using knockout (KO) mice, we have assessed the role of ICOSL in allergic airway inflammation and responsiveness using a standard mouse asthma model induced by ovalbumin (OVA) sensitization and challenge. Our data show that OVA-treated ICOSL KO mice exhibit significantly less lung eosinophilic infiltration, histopathology, mucus production and virtually no airway hyperresponsiveness in contrast to wild-type (Wt) counterparts. Serum antibody analysis showed that antigen-specific IgG1, IgG2a and IgE titers in ICOSL KO mice were significantly lower than those of Wt controls. Also, CD4(+) T cells isolated from ICOSL KO mice produced less T(h)2 cytokines (IL-4, IL-5, IL-10 and IL-13) but more T(h)1 (IFN-gamma) and IL-17 than their Wt controls. Taken together, we conclude that ICOSL plays an important role in predisposing individuals to allergic airway hyperresponsiveness by enhancing IgE antibody class switching and T(h)2 cytokine production and diminishing the T(h)17 response and airway eosinophilia.