Immunostimulatory oligonucleotides block allergic airway inflammation by inhibiting Th2 cell activation and IgE-mediated cytokine induction.
Immunostimulatory oligonucleotides block allergic airway inflammation by inhibiting Th2 cell activation and IgE-mediated cytokine induction.
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DOI：
10.1084/jem.20050631
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发表时间：
2005-12-05
期刊：
影响因子：
--
通讯作者：
Coffman RL
中科院分区：
文献类型：
--
作者：
Hessel EM;Chu M;Lizcano JO;Chang B;Herman N;Kell SA;Wills-Karp M;Coffman RL
在过敏原攻击前给予含cpg的免疫刺激DNA序列（ISS）单次治疗可以抑制过敏性哮喘动物模型中T辅助2型细胞（Th2）介导的气道反应；然而，这种抑制的机制在很大程度上仍未明确。在这里，我们证明了在th2启动的小鼠中，在过敏原攻击之前气道递送ISS以两种不同的方式防止对这种攻击的过敏反应。首先是防止诱导来自过敏原特异性Th2细胞的细胞因子，正如几乎完全抑制Th2细胞因子产生、Th2依赖性功能反应和基因诱导模式所证明的那样。ISS通过使肺抗原呈递细胞（APCs）不能有效地向Th2细胞呈递抗原而不是向Th1细胞呈递抗原来抑制Th2反应。APC功能的丧失与共刺激分子的表达减少有关，包括程序性细胞死亡配体（PD-L）1、PD-L2、CD40、CD80、CD86和诱导型T细胞共刺激剂，以及主要组织相容性复合体II类在iss处理小鼠气道CD11c+APC上的表达减少。ISS的第二个重要作用是抑制免疫球蛋白e依赖的Th2细胞因子的释放，特别是白细胞介素4，来自Th2启动小鼠气道中的嗜碱性细胞和/或肥大细胞。因此，ISS对过敏反应的抑制可以用两种新机制来解释，这两种新机制最终抑制了气道中2型细胞因子的主要来源。
A single treatment with a CpG-containing immunostimulatory DNA sequence (ISS) given before allergen challenge can inhibit T helper type 2 cell (Th2)–mediated airway responses in animal models of allergic asthma; however, the mechanism of this inhibition remains largely undefined. Here, we demonstrate that airway delivery of ISS before allergen challenge in Th2-primed mice acts in two distinct ways to prevent the allergic responses to this challenge. The first is to prevent induction of cytokines from allergen-specific Th2 cells, as demonstrated by the nearly complete inhibition of Th2 cytokine production, Th2-dependent functional responses, and gene induction patterns. ISS inhibits the Th2 response by rendering lung antigen-presenting cells (APCs) unable to effectively present antigen to Th2 cells, but not to Th1 cells. This loss of APC function correlates with a reduced expression of costimulatory molecules, including programmed cell death ligand (PD-L)1, PD-L2, CD40, CD80, CD86, and inducible T cell costimulator, and of major histocompatibility complex class II on CD11c+APCs from the airways of ISS-treated mice. The second important action of ISS is inhibition of immunoglobulin E–dependent release of Th2 cytokines, especially interleukin 4, from basophils and/or mast cells in the airways of Th2-primed mice. Thus, inhibition by ISS of allergic responses can be explained by two novel mechanisms that culminate in the inhibition of the principal sources of type 2 cytokines in the airways.
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影响因子：
4.4
作者：
Ford, JG;Rennick, D;Grünig, G
通讯作者：
Grünig, G
影响因子：
14.2
作者：
Chen, YH;Bieneman, AP;Schroeder, JT
通讯作者：
Schroeder, JT
DOI：
10.1164/rccm.200404-533oc
发表时间：
2004-12-01
影响因子：
24.7
作者：
Fanucchi, MV;Schelegle, ES;Miller, LA
通讯作者：
Miller, LA
影响因子：
4.4
作者：
Ikeda, RK;Miller, M;Broide, DH
通讯作者：
Broide, DH
影响因子：
14.2
作者：
Jain, VV;Kitagaki, K;Kline, JN
通讯作者：
Kline, JN