TLR-2 activation induces regulatory T cells and long-term suppression of asthma manifestations in mice.
TLR-2 activation induces regulatory T cells and long-term suppression of asthma manifestations in mice.
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DOI：
10.1371/journal.pone.0055307
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
van Oosterhout AJ
中科院分区：
文献类型：
--
作者：
Nawijn MC;Motta AC;Gras R;Shirinbak S;Maazi H;van Oosterhout AJ
哮喘是一种以气道阻塞和气道高反应性（AHR）为特征的慢性气道炎症性疾病。调节性T（Treg）细胞亚群对于免疫应答的调节至关重要。Treg细胞的连续转移已被证明足以抑制实验性过敏性哮喘中的气道炎症。因此，旨在扩大致敏个体气道中局部Treg细胞群的干预策略作为过敏性气道疾病的潜在治疗性治疗具有高度的意义。在这里，我们的目标是测试是否可以通过鼻内给予TLR-2激动剂局部扩增Treg细胞亚群来实现哮喘表现的长期抑制。为了模拟旨在扩大致敏宿主中内源性Treg群体的治疗性干预，我们通过OVA吸入伴随TLR-2激动剂Pam 3Cys的鼻内滴注来激发OVA致敏小鼠，然后进行额外的一系列OVA激发。Pam 3Cys治疗诱导哮喘表现的急性但短暂的加重，随后是乙酰甲胆碱的AHR降低或丧失，这取决于Pam 3Cys治疗和OVA激发之间的时间。此外，Pam 3Cys处理诱导肺浸润中嗜酸性粒细胞的显著减少和Treg细胞数量的增加。我们的数据显示，尽管具有不良的急性作用，但作为治疗干预的TLR 2激动剂治疗诱导肺中Treg细胞群的扩增，并导致在随后的过敏原激发后对过敏性哮喘表现的长期保护。我们的数据表明，局部扩大Tclase在过敏性气道疾病是一个有趣的治疗方法，值得进一步研究。
Asthma is a chronic inflammatory disease of the airways characterized by variable airway obstruction and airway hyperresponsiveness (AHR). The T regulatory (Treg) cell subset is critically important for the regulation of immune responses. Adoptive transfer of Treg cells has been shown to be sufficient for the suppression of airway inflammation in experimental allergic asthma. Intervention strategies aimed at expanding the Treg cell population locally in the airways of sensitized individuals are therefore of high interest as a potential therapeutic treatment for allergic airway disease. Here, we aim to test whether long-term suppression of asthma manifestations can be achieved by locally expanding the Treg cell subset via intranasal administration of a TLR-2 agonist. To model therapeutic intervention aimed at expanding the endogenous Treg population in a sensitized host, we challenged OVA-sensitized mice by OVA inhalation with concomitant intranasal instillation of the TLR-2 agonist Pam3Cys, followed by an additional series of OVA challenges. Pam3Cys treatment induced an acute but transient aggravation of asthma manifestations, followed by a reduction or loss of AHR to methacholine, depending on the time between Pam3Cys treatment and OVA challenges. In addition, Pam3Cys-treatment induced significant reductions of eosinophils and increased numbers of Treg cells in the lung infiltrates. Our data show that, despite having adverse acute effects, TLR2 agonist treatment as a therapeutic intervention induces an expansion of the Treg cell population in the lungs and results in long-term protection against manifestation of allergic asthma upon subsequent allergen provocation. Our data indicate that local expansion of Tregs in allergic airway disease is an interesting therapeutic approach that warrants further investigation.
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DOI：
10.1152/ajplung.00521.2007
发表时间：
2009-03-01
影响因子：
4.9
作者：
Burchell, Jennifer T.;Wikstrom, Matthew E.;Turner, Debra J.
通讯作者：
Turner, Debra J.
影响因子：
6.1
作者：
Maazi, H.;Shirinbak, S.;van Oosterhout, A. J. M.
通讯作者：
van Oosterhout, A. J. M.
DOI：
10.1165/rcmb.2009-0369oc
发表时间：
2011-08-01
影响因子：
6.4
作者：
Nawijn, Martijn C.;Piavaux, Benoit J. A.;Van Oosterhout, Antoon J. M.
通讯作者：
Van Oosterhout, Antoon J. M.
影响因子：
6.1
作者：
Boudousquie, C.;Pellaton, C.;Spertini, F.
通讯作者：
Spertini, F.
GITR信号传导通过在哮喘的小鼠模型中增强Th2细胞活性来增强气道高反应性。
影响因子：
5.8
作者：
Motta AC;Vissers JL;Gras R;Van Esch BC;Van Oosterhout AJ;Nawijn MC
通讯作者：
Nawijn MC