Pentraxin 3 deletion aggravates allergic inflammation through a T(H)17-dominant phenotype and enhanced CD4 T-cell survival.
Pentraxin 3 deletion aggravates allergic inflammation through a T(H)17-dominant phenotype and enhanced CD4 T-cell survival.
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DOI：
10.1016/j.jaci.2016.04.063
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Gounni AS
中科院分区：
文献类型：
--
作者：
Balhara J;Shan L;Zhang J;Muhuri A;Halayko AJ;Almiski MS;Doeing D;McConville J;Matzuk MM;Gounni AS
正五聚蛋白3（PTX 3）是一种多功能分子，在病原体清除、先天免疫系统、基质沉积、女性生育力和血管生物学之间的十字路口发挥非冗余作用。它由结构细胞和炎症细胞在感染和炎症部位产生。然而，其在过敏原诱导的炎症中的作用仍有待测试。我们试图确定Ptx 3缺失对卵清蛋白（OVA）诱导的哮喘小鼠模型过敏性炎症的影响。采用酶联免疫吸附法（ELISA）测定哮喘患者和健康对照者支气管肺泡灌洗液中PTX 3的含量。将Ptx 3 +/+和Ptx 3 −/−小鼠致敏，并用OVA和支气管肺泡灌洗液激发，并收集肺用于评估炎症。分别通过流式细胞术和苏木精和伊红以及高碘酸-希夫染色评估肺组织炎症和粘液产生。使用flexiVent测定这些小鼠中对乙酰甲胆碱的气道阻力。在这里，我们报告说，与健康对照小鼠相比，患有严重哮喘的小鼠和OVA致敏/激发的小鼠肺中的PTX 3水平增加。在OVA诱导的哮喘实验模型中，缺乏PTX 3的小鼠具有过度的嗜酸性/嗜酸性肺部炎症、粘液产生和气道高反应性。此外，暴露于OVA的肺Ptx 3 −/− CD 4 T细胞表现出IL-17 A的产生增加，这种作用伴随着信号转导和转录激活因子3磷酸化的增加，IL-2的产生减少，以及活化和存活的增强。此外，我们观察到与野生型对照小鼠相比，OVA暴露的Ptx 3 −/−小鼠中产生IL-6和IL-23的树突状细胞数量增加。总之，PTX 3缺乏导致气道高反应性增强、粘液产生和IL-17 A主导的肺部炎症，表明PTX 3在变应性炎症的发展中的调节作用。
Pentraxin 3 (PTX3) is a multifunctional molecule that plays a nonredundant role at the crossroads between pathogen clearance, innate immune system, matrix deposition, female fertility, and vascular biology. It is produced at sites of infection and inflammation by both structural and inflammatory cells. However, its role in allergen-induced inflammation remains to be tested. We sought to determine the effect of Ptx3 deletion on ovalbumin (OVA)–induced allergic inflammation in a murine model of asthma. Bronchoalveolar lavage fluid was collected from patients with severe asthma and healthy subjects, and the level of PTX3 was determined by using ELISA. Ptx3+/+ and Ptx3−/− mice were sensitized and challenged with OVA and bronchoalveolar lavage fluid, and the lungs were collected for assessing inflammation. Lung tissue inflammation and mucus production were assessed by means of flow cytometry and hematoxylin and eosin and periodic acid-Schiff staining, respectively. flexiVent was used to determine airway resistance to methacholine in these mice. Here we report that mice with severe asthma and OVA-sensitized/challenged mice had increased PTX3 levels in the lungs compared with healthy control mice. Mice lacking PTX3 have exaggerated neutrophilic/eosinophilic lung inflammation, mucus production, and airway hyperresponsiveness in an experimental model of OVA-induced asthma. Furthermore, OVA-exposed lung Ptx3−/− CD4 T cells exhibit an increased production of IL-17A, an effect that is accompanied by an increased signal transducer and activator of transcription 3 phosphorylation, reduced IL-2 production, and enhanced activation and survival. Also, we observed an increase in numbers of IL-6– and IL-23–producing dendritic cells in OVA-exposed Ptx3−/− mice compared with those in wild-type control mice. Altogether, PTX3 deficiency results in augmented airway hyperresponsiveness, mucus production, and IL-17A–dominant pulmonary inflammation, suggesting a regulatory role of PTX3 in the development of allergic inflammation.
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影响因子：
6.1
作者：
Cormican, L;O'Sullivan, S;Poulter, W
通讯作者：
Poulter, W
DOI：
10.1152/ajplung.1995.268.1.l117
发表时间：
1995-01-01
影响因子：
4.9
作者：
ERGER, RA;CASALE, TB
通讯作者：
CASALE, TB
影响因子：
4.4
作者：
Kadkhoda, Kamran;Wang, Shuhe;Yang, Xi
通讯作者：
Yang, Xi
DOI：
10.4049/jimmunol.0902185
发表时间：
2010-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Finkelman FD;Hogan SP;Hershey GK;Rothenberg ME;Wills-Karp M
通讯作者：
Wills-Karp M
影响因子：
4.8
作者：
Chen, Y;Thai, P;Wu, R
通讯作者：
Wu, R