Vascular endothelial growth factor is a key mediator in the development of T cell priming and its polarization to type 1 and type 17 T helper cells in the airways.
Vascular endothelial growth factor is a key mediator in the development of T cell priming and its polarization to type 1 and type 17 T helper cells in the airways.
复制标题
DOI：
10.4049/jimmunol.0901566
复制
发表时间：
2009-10-15
期刊：
影响因子：
--
通讯作者：
Kim YK
中科院分区：
文献类型：
--
作者：
Kim YS;Hong SW;Choi JP;Shin TS;Moon HG;Choi EJ;Jeon SG;Oh SY;Gho YS;Zhu Z;Kim YK
包括哮喘在内的慢性炎症性气道疾病的特征是对吸入过敏原的免疫功能障碍。我们之前的研究表明，T 细胞启动吸入过敏原需要 LPS，而 LPS 普遍存在于家庭灰尘过敏原中。在这项研究中，我们评估了血管内皮生长因子 (VEGF) 在 T 细胞启动发育中的作用，以及当暴露于 LPS 污染的过敏原时其极化为 Th1 或 Th17 细胞的作用。通过用LPS污染的过敏原使气道致敏来诱导哮喘小鼠模型，然后仅用过敏原进行攻击。在过敏原致敏期间进行治疗干预。本研究表明，IL-17 基因纯合破坏的小鼠中，由 LPS 污染的过敏原致敏引起的肺部炎症有所减少。此外，IL-6 敲除小鼠中过敏原特异性 Th17 免疫反应被消除。同时，气道暴露 LPS 上调了体内 VEGF 的产生。此外，过敏原加上重组 VEGF 的气道致敏诱导了 1 型和 17 型 Th 细胞（Th1 和 Th17）反应。在致敏期间用泛 VEGF 受体（VEGFR；VEGFR-1 加 VEGFR-2）抑制剂治疗可阻断由 LPS 污染的过敏原气道致敏诱导的 Th1 和 Th17 反应。这些效应伴随着 Th1 和 Th17 极化细胞因子 IL-12p70 和 IL-6 产生的抑制。这些发现表明，LPS 产生的 VEGF 在初始 T 细胞的激活以及随后分化为 Th1 和 Th17 细胞中发挥着关键作用。
Chronic inflammatory airway diseases including asthma are characterized by immune dysfunction to inhaled allergens. Our previous studies demonstrated that T cell priming to inhaled allergens requires LPS, which is ubiquitously present in household dust allergens. In this study, we evaluated the role of vascular endothelial growth factor (VEGF) in the development of T cell priming and its polarization to Th1 or Th17 cells when exposed to LPS-contaminated allergens. An asthma mouse model was induced by airway sensitization with LPS-contaminated allergens and then challenged with allergens alone. Therapeutic intervention was performed during allergen sensitization. The present study showed that lung inflammation induced by sensitization with LPS-contaminated allergens was decreased in mice with homozygous disruption of the IL-17 gene; in addition, allergen-specific Th17 immune response was abolished in IL-6 knockout mice. Meanwhile, in vivo production of VEGF was up-regulated by airway exposure of LPS. In addition, airway sensitization of allergen plus recombinant VEGF induced both type 1 and type 17 Th cell (Th1 and Th17) responses. Th1 and Th17 responses induced by airway sensitization with LPS-contaminated allergens were blocked by treatment with a pan-VEGF receptor (VEGFR; VEGFR-1 plus VEGFR-2) inhibitor during sensitization. These effects were accompanied by inhibition of the production of Th1 and Th17 polarizing cytokines, IL-12p70 and IL-6, respectively. These findings indicate that VEGF produced by LPS plays a key role in activation of naive T cells and subsequent polarization to Th1 and Th17 cells.
登录
查看更多内容
影响因子：
168.9
作者：
Asher, M. Innes;Montefort, Stephen;Williams, Hywel
通讯作者：
Williams, Hywel
DOI：
10.1084/jem.183.6.2593
发表时间：
1996-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fossiez F;Djossou O;Chomarat P;Flores-Romo L;Ait-Yahia S;Maat C;Pin JJ;Garrone P;Garcia E;Saeland S;Blanchard D;Gaillard C;Das Mahapatra B;Rouvier E;Golstein P;Banchereau J;Lebecque S
通讯作者：
Lebecque S
影响因子：
82.9
作者：
Lee, CG;Link, H;Elias, JA
通讯作者：
Elias, JA
影响因子：
168.9
作者：
Gereda, JE;Leung, DYM;Liu, AH
通讯作者：
Liu, AH
DOI：
10.1164/rccm.200310-1416oc
发表时间：
2005-02-01
影响因子：
24.7
作者：
Cho, SH;Stanciu, LA;Johnston, SL
通讯作者：
Johnston, SL