Deficiency of decorin induces expression of Foxp3 in CD4+CD25+ T cells in a murine model of allergic asthma
Deficiency of decorin induces expression of Foxp3 in CD4+CD25+ T cells in a murine model of allergic asthma
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DOI：
10.1111/resp.12485
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发表时间：
2015-08-01
期刊：
影响因子：
6.9
通讯作者：
Ludwig, Mara S.
中科院分区：
文献类型：
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作者：
Borges, Marcos C.;Narayanan, Venkatesan;Ludwig, Mara S.
背景与目的格调素（decorin, Dcn）是一种细胞外基质蛋白多糖，具有多种重要的生物学功能，其沉积在哮喘人和哮喘动物模型气道壁上发生改变。由于其对转化生长因子β (TGF)-的高亲和力，Dcn可以作为负反馈机制的一部分，从而调节该因子的生物利用度。Dcn缺陷（Dcn(-/-)）小鼠在反复的过敏原刺激下出现气道炎症、高反应性和重塑减少；我们研究了调节性T细胞是否在Dcn（-/-）小鼠气道反应减弱中发挥作用。方法用卵清蛋白（OVA）致敏sdcn（-/-）和Dcn（+/+）小鼠（C57Bl/6），每3天/周（x3周）鼻内攻毒。过敏原攻击后，收集支气管肺泡灌洗液，量化总细胞计数和分化细胞计数以及细胞因子水平。观察肺组织炎症细胞数量和细胞因子信使核糖核酸（mRNA）的产生。提取肺和脾细胞，评估调节性T细胞。结果ova刺激Dcn（+/+）小鼠组织炎症和白细胞介素(IL)-13 mRNA表达显著升高。在ova攻毒的Dcn（-/-）小鼠肺中CD4(+)CD25(+) T细胞中Foxp3表达升高，同时IL-10 mRNA表达升高。结论我们的数据表明，卵细胞攻击的Dcn（-/-）小鼠肺部炎症的减轻伴随着调节性T细胞和IL-10 mRNA水平的升高。这些结果加强了Dcn在生物过程中的重要性，特别是在哮喘过敏模型中。Decorin-deficient （Dcn(-/-)）小鼠出现气道炎症减少、高反应性和重塑。我们评估了调节性T细胞在Dcn（-/-）小鼠中的作用。Dcn(-/-) ova刺激小鼠的炎症减轻与气道上皮细胞磷酸化smad2染色、T细胞Foxp3表达和IL-10信使核糖核酸（mRNA）表达增加有关。
Background and objectiveDecorin (Dcn), an extracellular matrix proteoglycan, has several important biological functions, and its deposition is altered in the airway wall of humans with asthma and animal models of asthma. Due to its high affinity for transforming growth factor beta (TGF)-, Dcn can function as part of a negative feedback mechanism, resulting in the regulation of this factor's bioavailability. Dcn deficient (Dcn(-/-)) mice develop reduced airway inflammation, hyperresponsiveness and remodeling in response to repeated allergen challenge; we investigated whether regulatory T cells play a role in the diminished airway response of Dcn(-/-) mice.MethodsDcn(-/-) and Dcn(+/+) mice (C57Bl/6) were sensitized with ovalbumin (OVA) and challenged intra-nasally 3 days/weekx3 weeks. After allergen challenge, bronchoalveolar lavage was collected to quantify total and differential cell counts and cytokine levels. Inflammatory cell number and cytokine messenger ribonucleic acid (mRNA) production were assessed in lung tissues. Cells from lung and spleen were extracted to evaluate regulatory T cells.ResultsTissue inflammation and interleukin (IL)-13 mRNA expression were significantly increased in OVA-challenged Dcn(+/+) mice, only. The increased expression of Foxp3 in CD4(+)CD25(+) T cells found in lung of OVA-challenged Dcn(-/-) mice was accompanied by an increase in IL-10 mRNA.ConclusionsOur data demonstrated that a diminished lung inflammation in OVA challenged Dcn(-/-) mice was accompanied by a higher expression of regulatory T cells and IL-10 mRNA levels. These results reinforce the importance of Dcn in biological processes, particularly in an allergic model of asthma.Decorin-deficient (Dcn(-/-)) mice develop a reduced airway inflammation, hyperresponsiveness and remodelling. We evaluated the role of regulatory T cells in Dcn(-/-) mice. The diminished inflammation in Dcn(-/-) OVA-challenged mice was associated with an increase in airway epithelial cell phospho-Smad2 staining, Foxp3 expression in T cells and IL-10 messenger ribonucleic acid (mRNA) expression.