A regulatory CD9+ B-cell subset inhibits HDM-induced allergic airway inflammation
A regulatory CD9+ B-cell subset inhibits HDM-induced allergic airway inflammation
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DOI：
10.1111/all.12697
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发表时间：
2015-11-01
期刊：
影响因子：
12.4
通讯作者：
Brouard, S.
中科院分区：
文献类型：
--
作者：
Braza, F.;Chesne, J.;Brouard, S.
研究背景呼吸道变应原暴露可引起气道高反应性和炎症反应，其特征为T（H）2细胞的扩增和变应原特异性IgE的产生。过敏性哮喘的特征是免疫调节机制的改变，导致免疫系统促炎成分和抗炎成分之间的失衡。目的最近，B细胞被描述为炎症加剧的中枢调节因子，特别是在自身免疫的情况下。然而，在何种程度上这些细胞可以调节气道炎症和哮喘仍有待阐明。材料与方法我们利用过敏性哮喘模型诱导小鼠经皮致敏和呼吸挑战与提取物的屋尘螨。结果在这项研究中，我们发现，过敏性哮喘的诱导改变了IL-10（+）β的稳态，并有利于B细胞产生炎性细胞因子。进一步的转录组学和表型分析显示，它们富集在CD 9（+）B细胞亚群中。在哮喘小鼠中，过继转移CD 9（+）B细胞通过以IL-10依赖的方式抑制T（H）2和T（H）17驱动的炎症，恢复肺组织中有利的免疫平衡，使气道炎症和肺功能正常化。事实上，我们进一步表明，注射CD 9（+）BREG控制肺效应T细胞的扩张，允许建立一个有利的调节T细胞/效应T细胞的比例在lungs.ConclusionThis发现加强了潜在的Breg靶向治疗过敏性哮喘。
BackgroundExposure to respiratory allergens triggers airway hyperresponsiveness and inflammation characterized by the expansion of T(H)2 cells and the production of allergen specific IgE. Allergic asthma is characterized by an alteration in immune regulatory mechanisms leading to an imbalance between pro- and anti-inflammatory components of the immune system.AimsRecently B cells have been described as central regulators of exacerbated inflammation, notably in the case of autoimmunity. However, to what extent these cells can regulate airway inflammation and asthma remains to be elucidated.Materials & MethodsWe took advantage of a allergic asthma model in mice induced by percutaneous sensitization and respiratory challenge with an extract of house dust mite.ResultsIn this study, we showed that the induction of allergic asthma alters the homeostasis of IL-10(+) Bregs and favors the production of inflammatory cytokines by B cells. Deeper transcriptomic and phenotypic analysis of Bregs revealed that they were enriched in a CD9(+) B cell subset. In asthmatic mice the adoptive transfer of CD9(+) B cells normalized airway inflammation and lung function by inhibiting T(H)2- and T(H)17-driven inflammation in an IL-10-dependent manner, restoring a favorable immunological balance in lung tissues. Indeed we further showed that injection of CD9(+) Bregs controls the expansion of lung effector T cells allowing the establishment of a favorable regulatory T cells/effector T cells ratio in lungs.ConclusionThis finding strengthens the potential for Breg-targeted therapies in allergic asthma.