Allergen uptake, activation, and IL-23 production by pulmonary myeloid DCs drives airway hyperresponsiveness in asthma-susceptible mice.
Allergen uptake, activation, and IL-23 production by pulmonary myeloid DCs drives airway hyperresponsiveness in asthma-susceptible mice.
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DOI：
10.1371/journal.pone.0003879
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Wills-Karp, Marsha
中科院分区：
文献类型：
--
作者：
Lewkowich, Ian P.;Lajoie, Stephane;Clark, Jennifer R.;Herman, Nancy S.;Sproles, Alyssa A.;Wills-Karp, Marsha
适应性不良，th2极化炎症反应是过敏性哮喘发病机制的组成部分。作为T细胞活化的调节因子，树突状细胞（dc）是过敏性哮喘的重要介质，然而使内源性dc“促哮喘”的确切信号，以及这些信号在多大程度上受肺环境和宿主遗传学的调节，目前尚不清楚。对实验性哮喘易感（A/J）或耐药（C3H）小鼠肺DC群体的比较表型和功能分析显示，气道高反应性的易感性与髓系DC （mDC）过敏原的优先摄取和th17倾斜细胞因子（IL-6, IL-23）的产生有关，而耐药与浆细胞样DC的过敏原摄取增加有关。令人惊讶的是，将同源hdm脉冲骨髓来源的mDCs （bmdc）过继转移到C3H小鼠的肺部，显著提高了肺部IL-17A的产生，并使它们容易受到过敏原驱动的气道高反应性的影响。这些BMDCs的特征揭示了抗原摄取水平，Th17促进细胞因子产生的水平与易感A/J小鼠肺mDCs相似。总的来说，这些数据表明，哮喘抵抗小鼠的肺部环境促进了pDC过敏原的摄取和激活，并限制了th17扭曲的细胞因子的产生，这些细胞因子负责驱动病理性T细胞反应，这是过敏原诱导的气道高反应性的发展的核心。
Maladaptive, Th2-polarized inflammatory responses are integral to the pathogenesis of allergic asthma. As regulators of T cell activation, dendritic cells (DCs) are important mediators of allergic asthma, yet the precise signals which render endogenous DCs “pro-asthmatic”, and the extent to which these signals are regulated by the pulmonary environment and host genetics, remains unclear. Comparative phenotypic and functional analysis of pulmonary DC populations in mice susceptible (A/J), or resistant (C3H) to experimental asthma, revealed that susceptibility to airway hyperresponsiveness is associated with preferential myeloid DC (mDC) allergen uptake, and production of Th17-skewing cytokines (IL-6, IL-23), whereas resistance is associated with increased allergen uptake by plasmacytoid DCs. Surprisingly, adoptive transfer of syngeneic HDM-pulsed bone marrow derived mDCs (BMDCs) to the lungs of C3H mice markedly enhanced lung IL-17A production, and rendered them susceptible to allergen-driven airway hyperresponsiveness. Characterization of these BMDCs revealed levels of antigen uptake, and Th17 promoting cytokine production similar to that observed in pulmonary mDCs from susceptible A/J mice. Collectively these data demonstrate that the lung environment present in asthma-resistant mice promotes robust pDC allergen uptake, activation, and limits Th17-skewing cytokine production responsible for driving pathologic T cell responses central to the development of allergen-induced airway hyperresponsiveness.
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影响因子：
5.4
作者：
Hoshino, A;Tanaka, Y;Okumura, K
通讯作者：
Okumura, K
影响因子：
14.2
作者：
Faith, A;McDonald, J;Hawrylowicz, C
通讯作者：
Hawrylowicz, C
DOI：
10.1084/jem.20021328
发表时间：
2003-07-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Huh JC;Strickland DH;Jahnsen FL;Turner DJ;Thomas JA;Napoli S;Tobagus I;Stumbles PA;Sly PD;Holt PG
通讯作者：
Holt PG
影响因子：
4.4
作者：
Asselin-Paturel, C;Brizard, G;Trinchieri, G
通讯作者：
Trinchieri, G
影响因子：
30.5
作者：
Denning, Timothy L.;Wang, Yi-Chong;Pulendran, Bali
通讯作者：
Pulendran, Bali