OX40L induces helper T cell differentiation during cell immunity of asthma through PI3K/AKT and P38 MAPK signaling pathway.
OX40L induces helper T cell differentiation during cell immunity of asthma through PI3K/AKT and P38 MAPK signaling pathway.
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OX40L通过PI3K/AKT和P38 MAPK信号通路诱导哮喘细胞免疫过程中辅助T细胞分化
DOI：
10.1186/s12967-018-1436-4
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发表时间：
2018-03-20
影响因子：
7.4
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Huang L;Wang M;Yan Y;Gu W;Zhang X;Tan J;Sun H;Ji W;Chen Z
本研究旨在通过体外和体内实验探讨OX40L通过磷酸肌苷3激酶(PI3K)/AKT和p38丝裂原激活蛋白激酶信号通路调控辅助性T （Th）细胞分化的机制。方法采用哮喘患者和健康对照者的血清样本，探讨OX40L与Th细胞的关系。采用酶联免疫吸附法（ELISA）检测血清中OX40L、IL-4、IFN-γ、IL-17和TGF-β的浓度。流式细胞术检测Th1、Th2、Th17和Treg细胞。用3h -胸腺嘧啶测定T细胞的增殖。Western Blot检测蛋白表达和磷酸化水平。免疫组化法检测肺组织中OX40L的表达。结果患者血清中sox40l、IL-4、IL-17含量较正常对照组升高，卵清蛋白（OVA）引物单核细胞中IL-17含量较正常细胞升高，IFN-γ、TGF-β含量较正常细胞降低。此外，OX40L-Ig融合蛋白处理ova引发的CD4+T细胞可促进T细胞增殖、Th2和Th17细胞分化以及PI3K/AKT和p38 MAPK信号通路，抑制Th1和Treg细胞分化。此外，通过添加PI3K/AKT抑制、p38 MAPK抑制和抗ox40l单克隆抗体，可明显逆转ova诱导的CD4+T细胞的辅助性T细胞分化。结论本研究发现OX40L可通过PI3K/AKT和p38 MAPK信号通路调控哮喘患者辅助性T细胞的分化。此外，阻断OX40/OX40L可抑制CD4+T细胞的增殖，调节辅助性T细胞的极化。
BackgroundThe aim of this study was to investigate the mechanisms of OX40L in regulating helper T (Th) cells differentiation through phosphoinositide 3-kinase (PI3K)/AKT and p38 mitogen-activated protein kinase signaling pathway in vitro and in vivo experiments.MethodsSerum samples of patients with asthma and healthy controls were used to explore the association between OX40L and Th cells. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum concentrations of OX40L, IL-4, IFN-γ, IL-17 and TGF-β. Flow cytometry method was used to analyze Th1, Th2, Th17 and Treg cells. 3H-thymidine was used to determine the proliferation of T cells. Western Blot was used to detect protein expression and phosphorylation. Immunohistochemistry was used to detect the expression of OX40L in lung tissues.ResultsOX40L, IL-4, IL-17 increased in patient serum compared to healthy control and in the ovalbumin (OVA)-primed mononuclear cells compared to normal cells, while IFN-γ and TGF-β were decreased. Besides, the OVA-primed CD4+T cells treated with OX40L-Ig fusion protein promoted the proliferation of T cells and Th2 and Th17 cells differentiation as well as PI3K/AKT and p38 MAPK signaling pathway, but suppressed Th1 and Treg cells differentiation. Moreover, helper T cells differentiation in OVA-primed CD4+T cells could be markedly reversed by the addition of PI3K/AKT inhibition, p38 MAPK inhibition and anti-OX40L monoclonal antibody.ConclusionsIn this study, we revealed that OX40L could regulate differentiation of helper T cells via PI3K/AKT and p38 MAPK signaling pathway in asthma. Besides, blockade of OX40/OX40L could inhibit the proliferation of CD4+T cells and regulate polarization of helper T cells.
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影响因子：
5.8
作者：
Bosnjak B;Stelzmueller B;Erb KJ;Epstein MM
通讯作者：
Epstein MM
DOI：
10.4049/jimmunol.0904214
发表时间：
2010-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Naura AS;Zerfaoui M;Kim H;Abd Elmageed ZY;Rodriguez PC;Hans CP;Ju J;Errami Y;Park J;Ochoa AC;Boulares AH
通讯作者：
Boulares AH
影响因子：
14.2
作者：
Sagara, H;Okada, T;Nakao, A
通讯作者：
Nakao, A
影响因子：
5
作者：
Munoz, Lenka;Ramsay, Emma E.;Ammit, Alaina J.
通讯作者：
Ammit, Alaina J.
影响因子：
2.8
作者：
Ezzat, Mohamed Hesham Mohamed;Imam, Safaa Shafik;Elbrhami, Emhemed Mossbah
通讯作者：
Elbrhami, Emhemed Mossbah