Attenuation of allergen-induced airway hyperresponsiveness is mediated by airway regulatory T cells
Attenuation of allergen-induced airway hyperresponsiveness is mediated by airway regulatory T cells
复制标题
DOI：
10.1152/ajplung.00521.2007
复制
发表时间：
2009-03-01
影响因子：
4.9
通讯作者：
Turner, Debra J.
中科院分区：
文献类型：
--
作者：
Burchell, Jennifer T.;Wikstrom, Matthew E.;Turner, Debra J.
BurningJT，Wikstrom ME，Stumbles PA，Sly PD，Turner DJ。气道调节性T细胞介导变应原诱导的气道高反应性的减弱。美国生理学杂志肺细胞分子生理学296：L307-L319，2009年。首次发表于2008年11月21日; doi：10.1152/ajplung.00521.2007。了解吸入性过敏原的呼吸耐受机制可能会改善哮喘和过敏性疾病的治疗方法。气道高反应性（AHR）是过敏性哮喘的主要特征，因此本研究的目的是探讨慢性过敏原暴露过程中抑制过敏原诱导的AHR的机制。成年BALB/c小鼠用佐剂中的卵清蛋白（OVA）全身致敏，然后用单次3或6周的OVA气雾剂激发。在末次气雾剂吸入后24小时，评估气道和实质对吸入乙酰甲胆碱（MCh）的反应、炎症细胞计数、细胞因子、OVA特异性IgE和IgG（1）、实质组织学以及气道CD 4（+）69（+）活化和CD 4（+）25（-）FoxP 3（+）调节性T（Treg）细胞的数量。单次卵清蛋白激发导致AHR、嗜酸性粒细胞增多、血清卵清蛋白特异性IgE和支气管肺泡灌洗液（BAL）中辅助性T细胞2（Th 2）细胞因子增加，但与对照组小鼠相比，Treg数量无差异。与对照组小鼠相比，三周的OVA激发导致AHR受到抑制，气道Treg细胞数量增加，转化生长因子β（1）（TGF β（1））增加，尽管存在嗜酸性粒细胞增多，OVA特异性IgE和IgG（1）以及气道重塑。6周的卵清蛋白刺激恢复了AHR，而气道Treg数量、TGF β 1、BAL嗜酸性粒细胞增多和Th 2细胞因子恢复到对照水平。体内部分去除或过继转移Treg细胞分别恢复或抑制AHR，但不影响TGF β 1或Th 2细胞因子的产生。总之，AHR抑制是由气道Treg细胞介导的，并可能通过气道中TGF β 1的旁分泌诱导。
Burchell JT, Wikstrom ME, Stumbles PA, Sly PD, Turner DJ. Attenuation of allergen-induced airway hyperresponsiveness is mediated by airway regulatory T cells. Am J Physiol Lung Cell Mol Physiol 296: L307-L319, 2009. First published November 21, 2008; doi: 10.1152/ajplung.00521.2007.-Understanding the mechanisms involved in respiratory tolerance to inhaled allergens could potentially result in improved therapies for asthma and allergic diseases. Airway hyperresponsiveness (AHR) is a major feature of allergic asthma, thus the aim of the current study was to investigate mechanisms underlying suppression of allergen-induced AHR during chronic allergen exposure. Adult BALB/c mice were systemically sensitized with ovalbumin (OVA) in adjuvant and then challenged with a single 3 or 6 wk of OVA aerosols. Airway and parenchymal responses to inhaled methacholine (MCh), inflammatory cell counts, cytokines, OVA-specific IgE and IgG(1), parenchymal histology, and numbers of airway CD4(+)69(+) activated and CD4(+)25(-) FoxP3(+) regulatory T (Treg) cells were assessed 24 h after the final aerosol. Single OVA challenge resulted in AHR, eosinophilia, increased serum OVA-specific IgE, and T helper 2 (Th2) cytokines in bronchoalveolar lavage (BAL) but no difference in numbers of Treg compared with control mice. Three weeks of OVA challenges resulted in suppression of AHR and greater numbers of airway Treg cells and increased transforming growth factor-beta(1) (TGF beta(1)) compared with control mice despite the presence of increased eosinophilia, OVA-specific IgE and IgG(1), and airway remodeling. Six weeks of OVA challenges restored AHR, whereas airway Treg numbers, TGF beta(1), BAL eosinophilia, and Th2 cytokines returned to control levels. Partial in vivo depletion or adoptive transfer of Treg cells restored or inhibited AHR, respectively, but did not affect TGF beta(1) or Th2 cytokine production. In conclusion, AHR suppression is mediated by airway Treg cells and potentially via a paracrine induction of TGF beta(1) in the airways.