Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Mucosal Immunol. 2012 Jul;5(4):409-19. doi: 10.1038/mi.2012.18. Epub 2012 Apr 4.
To define the role of semaphorin 4A (Sema4A) in allergic response, we employed Sema4A⁻/⁻ and wild-type (WT) mice in the experimental model of ovalbumin (OVA)-induced allergic airway inflammation. We observed a selective increase in eosinophilic airway infiltration accompanied by bronchial epithelial cell hyperplasia in allergen-treated Sema4A⁻/⁻ mice relative to WT mice. This enhanced inflammatory response was associated with a selective increase in bronchoalveolar lavage (BAL) interleukin 13 (IL-13) content, augmented airway hyperreactivity, and lower regulatory T cell (Treg) numbers. In vivo allergen-primed Sema4A⁻/⁻ CD4+ T cells were more effective in transferring T helper type 2 (Th2) response to naive mice as compared with WT CD4+ T cells. T-cell proliferation and IL-13 productions in OVA₃₂₃₋₃₃₉-restimulated Sema4A⁻/⁻ cell cultures were upregulated. Generated bone marrow chimeras showed an equal importance of both lung-resident cell and inflammatory cell Sema4A expression in optimal disease regulation. These data provide a new insight into Sema4A biology and define Sema4A as an important regulator of Th2-driven lung pathophysiology.
为了定义信号蛋白 4A（Sema4A）在过敏反应中的作用，我们在卵清蛋白（OVA）诱导的过敏性气道炎症实验模型中使用 Sema4A⁻/⁻和野生型（WT）小鼠。我们观察到，与 WT 小鼠相比，过敏原处理的 Sema4A⁻/⁻小鼠中嗜酸性气道浸润伴有支气管上皮细胞增生呈选择性增加。这种增强的炎症反应与支气管肺泡灌洗液（BAL）白细胞介素 13（IL-13）含量的选择性增加、气道高反应性增强以及调节性 T 细胞（Treg）数量减少有关。与 WT CD4+T 细胞相比，体内过敏原致敏的 Sema4A⁻/⁻CD4+T 细胞在向幼稚小鼠转移 Th2 反应方面更有效。OVA₃₂₃₋₃₃₉刺激的 Sema4A⁻/⁻细胞培养物中的 T 细胞增殖和 IL-13 产生上调。生成的骨髓嵌合体表明，肺部驻留细胞和炎症细胞 Sema4A 的表达在最佳疾病调节中具有同等重要性。这些数据为 Sema4A 生物学提供了新的见解，并将 Sema4A 定义为 Th2 驱动的肺病理生理学的重要调节剂。
