Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen.

Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen.
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DOI:
10.1084/jem.20040035
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发表时间:
2004-07-05
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Lambrecht BN
Lambrecht BN
中科院分区:
其他
文献类型:
--
作者:
de Heer HJ;Hammad H;Soullié T;Hijdra D;Vos N;Willart MA;Hoogsteden HC;Lambrecht BN

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耐受性是吸入无害抗原的常见结果,但树突状细胞(dc)诱导的辅助性T (Th) 2型细胞对吸入过敏原的致敏在特应性哮喘中很常见。在这里,我们发现髓细胞dc (m)和浆细胞样dc (p)都吸收肺部吸入的抗原,并以免疫原性或耐受原性的形式将其呈递给引流淋巴结T细胞。引人注目的是,在吸入正常惰性抗原时,pDCs的消耗导致免疫球蛋白E致敏、气道嗜酸性粒细胞增多、杯状细胞增生和Th2细胞细胞因子的产生,这是哮喘的主要特征。此外,在小鼠哮喘模型中,致敏前过继性转移pDCs可预防疾病。在功能水平上,pDCs不诱导T细胞分裂,但抑制了mDCs诱导的效应T细胞的产生。这些研究表明,pDCs对无害抗原的炎症反应具有内在的保护作用。利用pDC功能的治疗方法可能在临床上有效地预防哮喘的发展。
Tolerance is the usual outcome of inhalation of harmless antigen, yet T helper (Th) type 2 cell sensitization to inhaled allergens induced by dendritic cells (DCs) is common in atopic asthma. Here, we show that both myeloid (m) and plasmacytoid (p) DCs take up inhaled antigen in the lung and present it in an immunogenic or tolerogenic form to draining node T cells. Strikingly, depletion of pDCs during inhalation of normally inert antigen led to immunoglobulin E sensitization, airway eosinophilia, goblet cell hyperplasia, and Th2 cell cytokine production, cardinal features of asthma. Furthermore, adoptive transfer of pDCs before sensitization prevented disease in a mouse asthma model. On a functional level, pDCs did not induce T cell division but suppressed the generation of effector T cells induced by mDCs. These studies show that pDCs provide intrinsic protection against inflammatory responses to harmless antigen. Therapies exploiting pDC function might be clinically effective in preventing the development of asthma.
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