Université de Nice-Sophia Antipolis, Valbonne, France.
Mucosal Immunol. 2011 May;4(3):343-53. doi: 10.1038/mi.2010.73. Epub 2010 Nov 3.
Allergic asthma is a T cell-dependent inflammatory lung disease that results from complex interactions between genetic predisposition and environmental factors, including exposure to lipopolysaccharide (LPS). In this study, we have shown that airway LPS exposure was sufficient to induce airway hyperreactivity (AHR) and eosinophil recruitment in mice that had previously experienced an acute episode of allergic asthma. LPS-induced disease reactivation depended on the activation of allergen-specific CD4(+) T cells by a subset of lung langerin(+) dendritic cells (DCs) that retained the allergen. Upon LPS exposure, migration of langerin(+) DCs from lungs to draining lymph nodes increased and LPS-exposed langerin(+) DCs instructed CD4(+) T cells toward a T helper (Th) 2 response. Selective depletion of langerin(+) DCs prevented LPS-induced eosinophil recruitment and T-cell activation, further demonstrating a critical role for langerin(+) DCs in disease reactivation. This finding provides a possible explanation for the subclinical worsening of asthmatics following exposure to low-dose LPS.
变应性哮喘是一种 T 细胞依赖性炎症性肺部疾病，是遗传易感性和环境因素（包括脂多糖[LPS]暴露）之间复杂相互作用的结果。在这项研究中，我们表明，气道 LPS 暴露足以在先前经历过急性变应性哮喘发作的小鼠中诱导气道高反应性（AHR）和嗜酸性粒细胞募集。LPS 诱导的疾病再激活取决于先前经历过急性变应性哮喘发作的小鼠中，一组肺朗格汉斯细胞（ langerin ）+树突状细胞（DC）通过激活过敏原特异性 CD4+T 细胞。在 LPS 暴露后，从肺部迁移到引流淋巴结的 langerin+DC 增加，并且 LPS 暴露的 langerin+DC 指导 CD4+T 细胞向 Th2 反应。选择性耗尽 langerin+DC 可防止 LPS 诱导的嗜酸性粒细胞募集和 T 细胞激活，进一步证明 langerin+DC 在疾病再激活中起关键作用。这一发现为哮喘患者接触低剂量 LPS 后亚临床恶化提供了一种可能的解释。
