哮喘患儿鼻病毒A和C刺激淋巴细胞的差异基因表达

2020/03/11

   摘要
   原理:哮喘患者对鼻病毒的抗体应答增强,但C型鼻病毒(RV)的抗体应答低于A型鼻病毒,提示对C型鼻病毒的免疫力较差。
   目的:目的探讨和比较RV-A和RV-C对哮喘患儿和非哮喘患儿的t细胞记忆反应。
   方法:用肽制剂体外刺激17名哮喘患儿和19名非哮喘对照组的外周血单核细胞,诱导其对RV-A和RV-C有代表性的种特异性反应。分子分析(RNA-Seq)被用来识别富集途径和上游调节因子。
   结果:RV-A反应中IFNG和STAT1的表达高于RV-C,而CXCL9、10和11的显著表达在RV-C反应中未发现。Th2细胞因子基因或Th2趋化因子基因CCL11、CCL17、CCL22无相互增加。在非哮喘和哮喘患者反应中RV-C诱导CCL24(eotaxin-2)的表达均高于RV-A。上游调节因子分析显示,RV-A和RV-C均可诱导Th1和炎性细胞因子的显著表达,但程度较轻。与非哮喘患者相比,哮喘患者对RV-A和RV-C的反应均较低,但保留了每个物种的基因表达模式和上游调节因子的特征。各组均显示IL-17A通路激活。
   结论:与没有Th2上调的RV-A相比,RV-C诱导的记忆细胞具有更低的IFN-γ型应答。 与非哮喘病相比,哮喘患者的记忆效应更低,但每个物种的激活谱在很大程度上基本保持不变。 因此,RV-A和RV-C诱导出不同的T细胞反应。

 
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校 )
(Am. J. Respir. Crit. Care Med. 2020 Mar 06)


 
 
Differential Gene Expression of Lymphocytes Stimulated with Rhinovirus A and C in Asthmatic Children.
 
Anderson D, Jones AC, Gaido CM, Carter KW, Laing IA, Bosco A, Thomas WR, Hales BJ,
 
Abstract
RATIONALE:Asthmatics have heightened antibody responses to rhinovirus although those specific for rhinovirus C are lower than responses specific for rhinovirus A suggesting poor immunity to this species.
OBJECTIVES:To ascertain and compare T-cell memory responses induced by RV-A and RV-C in asthmatic and non-asthmatic children.
METHODS:Peripheral blood mononuclear cells from 17 asthmatic children and 19 non-asthmatic controls were stimulated in vitro with peptide formulations to induce representative species-specific responses to RV-A and RV-C. Molecular profiling (RNA-Seq) was used to identify enriched pathways and upstream regulators.
MEASUREMENTS AND MAIN RESULTS:Responses to RV-A showed higher expression of IFNG and STAT1 compared to RV-C and significant expression of CXCL9, 10 and 11 not found for RV-C. There was no reciprocal increase of Th2 cytokine genes or the Th2 chemokine genes CCL11, CCL17 and CCL22. RV-C induced higher expression of CCL24 (eotaxin-2) than RV-A in the responses of both non-asthmatic and asthmatics. Upstream regulator analysis showed both RV-A and, although to a lesser extent, RV-C induced predominant Th1 and inflammatory cytokine expression. The responses of asthmatics compared to non-asthmatics were lower for both RV-A and RV-C while retaining the pattern of gene expression and upstream regulators characteristic of each species. All groups showed activation of the IL-17A pathway.
CONCLUSIONS:RV-C induced memory cells with a lower IFN-γ type response than RV-A without Th2 upregulation. Asthmatics had lower recall responses than non-asthmatics while largely retaining the same gene activation profile for each species. RV-A and RV-C therefore induce qualitatively different T-cell responses.




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