过敏性紫癜患儿外周血单个核细胞 TLR2、TLR4表达及其与 Th1和 Th2型免疫应答相关性观察  

Study on the expression of TLR2 and TLR4 in peripheral blood mononuclear cells and their relation- ship with Th1/Th2 immune response in patients with Henoch-Schonlein purpura

作　　者：常红[1] 张秋业[1] 程娜[2] 张守青[1] 林毅[1] 

机构地区：[1]青岛大学医学院附属医院心肾免疫儿科,266003 [2]山东省千佛山医院儿科

出　　处：《中华微生物学和免疫学杂志》2013年第11期839-844,共6页Chinese Journal of Microbiology and Immunology

基　　金：山东省优秀中青年科学家科研奖励基金（BS2011SW006）;山东省医药卫生科技发展计划项目（2011HW029）

摘　　要：目的：研究Toll样受体（Toll-like receptor，TLR）2、TLR4在过敏性紫癜（HSP）患儿外周血单核细胞的表达及其与Th1和Th2型免疫应答的相关性，探讨TLR2、TLR4在HSP发病机制中的作用。方法选取2011年10月-2012年11月于我院儿内科收治的HSP患儿64例为研究对象，分为HSP无肾损害组（NHSPN，36例）及HSP有肾损害组（HSPN，28例），另选取我院儿保科健康查体儿童30例作为正常对照组。采用流式细胞术检测外周血T淋巴细胞亚群及单核细胞TLR2及TLR4蛋白表达，实时荧光定量PCR技术检测外周血单核细胞TLR2 mRNA及TLR4 mRNA的基因相对表达量，ELISA法检测血浆IFN-γ、IL-4、IL-6水平。结果（1） HSP 患儿外周血单核细胞TLR2 mRNA、TLR4 mRNA相对表达量及TLR2、TLR4蛋白表达均显著高于正常对照组（P均＜0．01），HSPN组外周血单核细胞TLR2 mRNA、TLR4 mRNA相对表达量及TLR2、TLR4蛋白表达均明显高于NHSPN组（P＜0．05；P＜0．01；P＜0．01；P＜0．01）。（2）HSP组CD3＋T细胞、CD3＋CD4＋T细胞显著降低，CD3＋CD8＋T细胞及CD3＋HLADR＋活化T细胞明显升高（P均＜0．01）。（3）HSP组血浆IL-4、IL-6水平显著高于正常对照组（P＜0．01，P＜0．01），IFN-γ水平显著低于正常对照组（P＜0．05），IFN-γ/IL-4比值显著低于对照组（P＜0．01）。（4）HSP组TLR2、TLR4蛋白表达与血浆IL-4、IL-6水平均呈显著正相关（P＜0．01，P＜0．05；P＜0．01，P＜0．01）；与IFN-γ/IL-4比值均呈显著负相关（P＜0．01；P＜0．01）。结论TLR2及TLR4活化可能参与了HSP的免疫发病机制，TLR2及TLR4的过度活化可能与HSP的肾损伤有关。 HSP患儿存在T淋巴细胞亚群失调，功能紊乱，Th1/Th2失衡。活化的TLR2及TLR4可能通过上调Th2型免疫应答介导HSP的免疫发病机制。Objective To explore the role of TLR2 and TLR4 in the pathogenesis of Henoch-Schonlein purpura （ HSP） by investigating their expression at mRNA and protein levels in peripheral blood mononuclear cells （ PBMCs ） and their influences on Th 1/Th2 immune response in children with HSP . Methods 64 hospitalized children with HSP in the Affiliated Hospital of Qingdao University Medical Col -lege from October 2011 to November 2012 were enrolled in the study .They were further divided into non-He-noch-Schonlein purpura nephritis （ NHSPN ） group （ n =36 ） and Henoch-Schonlein purpura nephritis （HSPN） group （n=28）.30 age-matched healthy children from Child Health Division of the same hospital were selected as controls .The expression of TLR2 and TLR4 at mRNA level in PBMCs were detected by re-al-time fluorescent polymerase chain reaction .The expression of TLR2 and TLR4 at protein level and T cells subset were detected by flow cytometry .The levels of IFN-γ, IL-4 and IL-6 in plasma were determined by enzyme-linked immunosorbent assay （ELISA）.Results （1）Compared with the control group , the expres-sion of TLR2 and TLR4 at mRNA and protein levels were remarkably increased in children with HSP , espe-cially in HSPN group.（2）Compared with the control group, the percentage of CD3＋T cells and CD3＋CD4＋T cells were down-regulated in HSP group , but the percentage of CD 3＋CD8＋T cells and CD3＋HLADR＋T cells were up-regulated.（3）The level of IFN-γand the ratio of IFN-γ/IL-4 in plasma from children with HSP were significantly lower than those of the controls , while the level of IL-4 and IL-6 were remarkably higher than those of the controls .（4）The expression of TLR2 and TLR4 at protein level in PBMCs from chil-dren with HSP showed significant positive correlations with the expression of TLR 2 and TLR4 at mRNA level and plasma concentration of IL-4 and IL-6, but a negative correlation with the ratio of IFN-γ/IL-4.Conclu-sions The aberrant activation of TLR 2 and TLR4 might b

关 键 词：过敏性紫癜 儿童 TOLL样受体 IFN-γ IL-4 

分 类 号：R725.5[医药卫生—儿科]