Activin A and TGF-β promote T(H)9 cell-mediated pulmonary allergic pathology.
Activin A and TGF-β promote T(H)9 cell-mediated pulmonary allergic pathology.
复制标题
DOI：
10.1016/j.jaci.2011.12.965
复制
发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Lloyd CM
中科院分区：
文献类型：
--
作者：
Jones CP;Gregory LG;Causton B;Campbell GA;Lloyd CM
IL-9分泌型（TH 9）T细胞被认为是一个独特的T细胞亚群。然而，其在疾病中的功能的证据是不确定的。定义TH 9驱动的体内病理学的功能表型。我们使用荧光激活细胞分选来识别特应性和非特应性受试者中的循环TH 9细胞。在小鼠中，我们利用屋尘螨诱导的过敏性气道疾病模型来确定体内TH 9细胞功能以及激活素A在TH 9产生中的作用。与非特应性供体相比，过敏性患者具有升高的TH 9细胞数量，这与升高的IgE水平相关。在鼠模型中，用屋尘螨的过敏原攻击导致快速的TH 9分化和增殖，其动力学比TH 2细胞分化快得多，导致肥大细胞的特异性募集和活化。TGF-β超家族成员激活素A复制TGF-β1在驱动TH 9细胞体外生成中的功能。重要的是，只有当激活素A和TGF-β联合阻断而不是单独阻断时，才能实现对变应原诱导的TH 9分化的体内抑制，从而导致气道高反应性和胶原沉积减少。相反，TH 9细胞的过继转移导致病理学增强。我们的数据确定了TH 9细胞的独特功能作用，并概述了它们在体外和体内产生的新途径。在功能上，TH 9细胞促进过敏反应，导致由肺中肥大细胞的特异性募集和活化介导的病理学增强。
IL-9-secreting (TH9) T cells are thought to represent a distinct T-cell subset. However, evidence for their functionality in disease is uncertain. To define a functional phenotype for TH9-driven pathology in vivo. We used fluorescence-activated cell sorting to identify circulating TH9 cells in atopic and nonatopic subjects. In mice we utilized a model of allergic airways disease induced by house dust mite to determine TH9 cell function in vivo and the role of activin A in TH9 generation. Allergic patients have elevated TH9 cell numbers in comparison to nonatopic donors, which correlates with elevated IgE levels. In a murine model, allergen challenge with house dust mite leads to rapid TH9 differentiation and proliferation, with much faster kinetics than for TH2 cell differentiation, resulting in the specific recruitment and activation of mast cells. The TGF-β superfamily member activin A replicates the function of TGF-β1 in driving the in vitro generation of TH9 cells. Importantly, the in vivo inhibition of TH9 differentiation induced by allergen was achieved only when activin A and TGF-β were blocked in conjunction but not alone, resulting in reduced airway hyperreactivity and collagen deposition. Conversely, adoptive transfer of TH9 cells results in enhanced pathology. Our data identify a distinct functional role for TH9 cells and outline a novel pathway for their generation in vitro and in vivo. Functionally, TH9 cells promote allergic responses resulting in enhanced pathology mediated by the specific recruitment and activation of mast cells in the lungs.
登录
查看更多内容
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
4.8
作者：
Funaba, M;Ikeda, T;Abe, M
通讯作者：
Abe, M
DOI：
10.1165/ajrcmb.19.5.3457
发表时间：
1998-11-01
影响因子：
6.4
作者：
McLane, MP;Haczku, A;Levitt, RC
通讯作者：
Levitt, RC
DOI：
10.1016/j.jaci.2009.06.022
发表时间：
2009-09
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Kariyawasam HH;Pegorier S;Barkans J;Xanthou G;Aizen M;Ying S;Kay AB;Lloyd CM;Robinson DS
通讯作者：
Robinson DS
DOI：
10.1038/nri2848
发表时间：
2010-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--