背景：我们在分子水平对过敏性哮喘的严重程度和持续性的决定性因素了解较少。细胞因子信号1抑制因子（SOCS1）是体外IL-4依赖性的信号通路的负向调节因子，能控制Th2型免疫反应，如IgE水平、粘蛋白产生、IL-5和IL-13诱导以及粘膜嗜酸性粒细胞性炎症，这些都是过敏性哮喘的病理生理学表现。
目的：本文在亚慢性雾化致敏诱导的小鼠哮喘模型中，研究SOCS1在调节Th2相关性疾病特点中的作用。
方法：致敏并给予卵清蛋白（OVA）后，收集IFN-γ和Socs1基因敲除小鼠（Socs1(-/-)Ifnγ(-/-)）的支气管肺泡灌洗液和血清。分析肺浸润细胞的组成、血清IgE和IgG1及细胞因子水平。
结果：与单IFN-γ基因敲除（Ifnγ(-/-)）和正常C57BL/6小鼠相比，Socs1(-/-)Ifnγ(-/-)小鼠OVA处理后血清IgE水平和肺浸润嗜酸性细胞显著增加。OVA 处理过的Socs1(-/-)Ifnγ(-/-)小鼠的CD4+细胞及肺组织Th2细胞因子、IL-4、IL-5和IL-13表达显著增加。在生理盐水处理的Socs1(-/-)Ifnγ(-/-)小鼠，IgE、IL-5水平及浸润的嗜酸性细胞同样有所增加，表明缺少SOCS1，小鼠Th2反应存在缺陷。目前还不清楚细胞因子水平的上升是否会加重OVA致敏后Th2细胞功能受损，或细胞内信号增强是否加重Th2细胞功能受损。在所检测的不同的IL-4/IL-13应答基因中，致敏的Socs1(-/-)Ifnγ(-/-)小鼠中肺内仅I型精氨酸酶轻度上调，表明SOCS1的调节主要针对造血细胞，而不是呼吸道上皮细胞。
结论：综合上述结果，SOCS1是Th2反应的重要调节因子。
（刘国梁 审校）
LEE C. et al, Clin Exp Allergy. 2009 Mar 20. [Epub ahead of print]
Suppressor of cytokine signalling 1 (SOCS1) is a physiological regulator of the asthma response.
Background： The molecular determinants of the severity and persistence of allergic asthma remain poorly understood. Suppressor of cytokine signalling 1 (SOCS1) is a negative regulator of IL-4-dependent pathways in vitro and might therefore control T-helper type 2 (Th2) immunity associated traits, such as IgE levels, mucin production, IL-5 and IL-13 induction, and eosinophilic mucosal inflammation, which are implicated in allergic asthma.
Objective： To investigate the role of SOCS1 in regulating Th2-associated disease traits in a murine sub-chronic aeroallergen-driven asthma model.
Methods： Following sensitization and challenge with ovalbumin (OVA), bronchoalveolar lavage and serum were collected from mice lacking the Socs1 gene on an IFN-gamma null background (Socs1(-/-)Ifngamma(-/-)). The composition of infiltrating cells in the lung, serum IgE and IgG1 levels and cytokine levels were analysed. Results Serum IgE levels and infiltrating eosinophils were considerably increased in the lungs of OVA-treated Socs1(-/-)Ifngamma(-/-) mice compared with Ifngamma(-/-) and C57BL/6 controls. Expression of the Th2 cytokines, IL-4, IL-5 and IL-13 was increased in CD4(+) cells and lung tissue from OVA-treated Socs1(-/-)Ifngamma(-/-) mice. IgE, IL-5 levels and infiltrating eosinophils were also elevated in saline-treated Socs1(-/-)Ifngamma(-/-) mice, suggesting that in the absence of SOCS1, mice are already biased towards a Th2 response. It is at present unclear whether the elevated cytokine levels are sufficient to result in the exacerbated Th2 response to OVA challenge or whether enhanced intra-cellular signalling also contributes. Surprisingly, of the various IL-4/IL-13 responsive genes tested, only Arginase I appeared to be modestly up-regulated in the lungs of OVA-treated Socs1(-/-)Ifngamma(-/-) mice, suggesting that regulation by SOCS1 occurs primarily in haematopoietic cells and not in the airway epithelium.
Conclusions： Together these results indicate that SOCS1 is an important regulator of the Th2 response.
