系统性红斑狼疮病人外周血浆细胞样树突状细胞中Toll样受体7的表达及其意义
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摘要
目的:检测系统性红斑狼疮(SLE)病人外周血中浆细胞样树突状细胞(pDC)中Toll样受体7(TLR7)的表达,探讨其意义。方法:选取SLE病人52例(SLE组)和正常健康人28名(对照组),利用流式细胞术检测外周血TLR7+的pDC细胞在各组中的比例。结果:SLE病人外周血单核细胞(PBMC)中pDC相对计数显著低于对照组(P<0.01),SLE组和正常对照组髓样树突状细胞水平差异无统计学意义(P>0.05)。感染组SLE病人外周血pDC水平显著低于非感染组(P<0.01),初发组SLE病人外周血髓样树突状细胞水平低于复发组(P<0.05),pDC水平与外周血CRP呈负相关关系(P<0.05)。SLE病人外周血PBMC内pDC中TLR7+细胞的比例显著高于对照组(P<0.01)。血液系统受累组pDC内TLR7+细胞比例高于无血液系统受累组(P<0.05)。TLR7+pDC细胞比例在抗ds DNA抗体、抗Sm抗体、抗SSA抗体、抗SSB抗体阳性组及阴性组之间差异均无统计学意义(P>0.05);TLR7+pDC细胞比例和蛋白尿分级呈显著正相关关系(P<0.01)。结论:SLE病人外周血TLR7+的pDC细胞比例显著升高,且与临床病情活动性有一定的相关性。
Objective:To investigate the expression of Toll like receptor 7(TLR7) in peripheral plasmacytoid dendritic cells(pDC) of patients with systemic lupus erythematosus(SLE),and its significance.Methods:Fifty two patients with SLE and 28 healthy persons were divided into the SLE group and control group,respectively.The proportion of TLR7 + pDC in peripheral blood were measured using flow cytometry.Results:The relative count of pDC in peripheral blood monouclear cells(PBMC) of SLE patients was significantly lower than that in control group(P<0.01),and there was no statistical significance in the relative count of myeloid dendritic cells(m DC) between SLE group and control group(P>0.05).The level of peripheral blood pDC in SLE patients was significantly lower than that in non-infected patients(P<0.01),and the level of peripheral blood m DC in patients with primary SLE was lower than that in recurrent patients(P<0.05),and there was a negative correlation between pDC level and CRP(P<0.05).The proportion of TLR7+pDC in peripheral blood in SLE patients was significantly higher than that in control group(P<0.01).The proportion of TLR7 + pDC of SLE patients with hematological involvement was higher than that in patients without hematological involvement(P<0.05).There was no statistical significance in the proportion of TLR7 + pDC between anti ds DNA antibody,anti Sm antibody,anti SSA antibody,anti SSB antibody positive group and negative group(P>0.05).There was a positive correlation between the proportion of TLR7 + pDC and grade of proteinuria(P<0.01).Conclusions:The proportion of TLR7+pDC in peripheral blood of patients with SLE significantly increases,and which is correlated with the disease activity.
Objective:To investigate the expression of Toll like receptor 7(TLR7) in peripheral plasmacytoid dendritic cells(pDC) of patients with systemic lupus erythematosus(SLE),and its significance.Methods:Fifty two patients with SLE and 28 healthy persons were divided into the SLE group and control group,respectively.The proportion of TLR7 + pDC in peripheral blood were measured using flow cytometry.Results:The relative count of pDC in peripheral blood monouclear cells(PBMC) of SLE patients was significantly lower than that in control group(P<0.01),and there was no statistical significance in the relative count of myeloid dendritic cells(m DC) between SLE group and control group(P>0.05).The level of peripheral blood pDC in SLE patients was significantly lower than that in non-infected patients(P<0.01),and the level of peripheral blood m DC in patients with primary SLE was lower than that in recurrent patients(P<0.05),and there was a negative correlation between pDC level and CRP(P<0.05).The proportion of TLR7+pDC in peripheral blood in SLE patients was significantly higher than that in control group(P<0.01).The proportion of TLR7 + pDC of SLE patients with hematological involvement was higher than that in patients without hematological involvement(P<0.05).There was no statistical significance in the proportion of TLR7 + pDC between anti ds DNA antibody,anti Sm antibody,anti SSA antibody,anti SSB antibody positive group and negative group(P>0.05).There was a positive correlation between the proportion of TLR7 + pDC and grade of proteinuria(P<0.01).Conclusions:The proportion of TLR7+pDC in peripheral blood of patients with SLE significantly increases,and which is correlated with the disease activity.
引文
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[13]CELHAR T,YASUGA H,LEE HY,et al.TLR9 deficiency breaks tolerance to RNA-associated antigens and upregulates TLR7 protein in Sle1 mice[J].Arthritis Rheumatol,2018.
[14]TAKAGI H,ARIMURA K,UTO T,et al.Plasmacytoid dendritic cells orchestrate TLR7-mediated innate and adaptive immunity for the initiation of autoimmune inflammation[J].Scientific Reports,2016,6:24477.
[15]赵小娟,汪国生,俞大亮,等.系统性红斑狼疮患者外周血树突状细胞的变化及意义[J].安徽医科大学学报,2012,47(8):948.
[16]WORBS T,HAMMERSCHMIDT SI.Dendritic cell migration in health and disease[J].Nat Rev Immunol,2017,17(1):30.
[17]JIN O,KAVIKONDALA S,SUN L,et al.Systemic lupus erythematosus patients have increased number of circulating plasmacytoid dendritic cells,but decreased myeloid dendritic cells with deficient CD83 expression[J].Lupus,2008,17(7):654.
[18]郭文静,陈琳洁,李志军,等.系统性红斑狼疮患者外周血浆细胞样树突状细胞的变化及意义[J].蚌埠医学院学报,2016,41(8):995.
[19]MURAYAMA G,FURUSAWA N,CHIBA A,et al.Enhanced IFN-αproduction is associated with increased TLR7 retention in the lysosomes of palasmacytoid dendritic cells in systemic lupus erythematosus[J].Arthritis Research Therapy,2017,19(1):234.
[20]LYN-COOK BD,XIE C,OATES J,et al.Increased expression of Toll-like receptors(TLRs)7 and 9 and other cytokines in systemic lupus erythematosus(SLE)patients:ethnic differences and potential new targets for therapeutic drugs[J].Mol Immunol,2014,61(1):38.
[21]SISIRAK V,GANGULY D,LEWIS KL,et al.Genetic evidence for the role of plasmacytoid dendritic cells in systemic lupus erythematosus[J].J Exp Med,2014,211(10):1969.
[22]ROWLAND SL,RIGGS JM,GILFILLAN S,et al.Early,transient depletion of plasmacytoid dendritic cells ameliorates autoimmunity in a lupus model[J].J Exp Med,2011,211(10):1977.
[2]SWIECKI M,COLONNA M.The multifaceted biology of plasmacytoid dendritic cells[J].Nat Rev Immunol,2015,15(8):471.
[3]RNNBLOM L.The importance of the type I interferon system in autoimmunity[J].Clin Exp Rheumatol,2016,34(4 Suppl 98):21.
[4]LIU Z,DAVIDSON A.Taming lupus—a new understanding of pathogenesis is leading to clinical advances[J].Nat Med,2012,18(6):871.
[5]CHRISTENSEN SR,SHUPE J,NICKERSON K,et al.Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus[J].Immunity,2006,25(3):417.
[6]NICKERSON KM,CHRISTENSEN SR,SHUPE J,et al.TLR9regulates TLR7-and My D88-dependent autoantibody production and disease in a murine model of lupus[J].J Immunol,2010,184(4):1840.
[7]王涛,李志军,李柏青.等.Toll样受体7及9在系统性红斑狼疮患者外周血B淋巴细胞内的表达及意义[J].中华风湿病学杂志,2009,13(8):560.
[8]ACHEK A,YESUDHAS D.Toll-like receptors:promising therapeutic targets for inflammatory diseases[J].Arch Pharm Res,2016,39(8):1032.
[9]CLANCY RM,MARKHAM AJ,BUYON JP.Endosomal Toll-like receptors in clinically overt and silent autoimmunity[J].Immunol Rev,2016,269(1):76.
[10]CELHAR T,FAIRHURST AM.Toll-like receptors in systemic lupus erythematosus:potential for personalized treatment[J].Front Pharmacol,2014,5(5):265.
[11]FUKUI R,SAITOH S,KANNO A,et al.Unc93B1 restricts systemic lethal inflammation by orchestrating Toll-like receptor 7 and9 trafficking[J].Immunity,2011,35(1):69.
[12]YOKOGAWA M,TAKAISHI M,NAKAJIMA K,et al.Epicutaneous application of toll-like receptor 7 agonists leads to systemic autoimmunity in wild-type mice:a new model of systemic Lupus erythematosus[J].Arthritis Rheumatol,2014,66(3):694.
[13]CELHAR T,YASUGA H,LEE HY,et al.TLR9 deficiency breaks tolerance to RNA-associated antigens and upregulates TLR7 protein in Sle1 mice[J].Arthritis Rheumatol,2018.
[14]TAKAGI H,ARIMURA K,UTO T,et al.Plasmacytoid dendritic cells orchestrate TLR7-mediated innate and adaptive immunity for the initiation of autoimmune inflammation[J].Scientific Reports,2016,6:24477.
[15]赵小娟,汪国生,俞大亮,等.系统性红斑狼疮患者外周血树突状细胞的变化及意义[J].安徽医科大学学报,2012,47(8):948.
[16]WORBS T,HAMMERSCHMIDT SI.Dendritic cell migration in health and disease[J].Nat Rev Immunol,2017,17(1):30.
[17]JIN O,KAVIKONDALA S,SUN L,et al.Systemic lupus erythematosus patients have increased number of circulating plasmacytoid dendritic cells,but decreased myeloid dendritic cells with deficient CD83 expression[J].Lupus,2008,17(7):654.
[18]郭文静,陈琳洁,李志军,等.系统性红斑狼疮患者外周血浆细胞样树突状细胞的变化及意义[J].蚌埠医学院学报,2016,41(8):995.
[19]MURAYAMA G,FURUSAWA N,CHIBA A,et al.Enhanced IFN-αproduction is associated with increased TLR7 retention in the lysosomes of palasmacytoid dendritic cells in systemic lupus erythematosus[J].Arthritis Research Therapy,2017,19(1):234.
[20]LYN-COOK BD,XIE C,OATES J,et al.Increased expression of Toll-like receptors(TLRs)7 and 9 and other cytokines in systemic lupus erythematosus(SLE)patients:ethnic differences and potential new targets for therapeutic drugs[J].Mol Immunol,2014,61(1):38.
[21]SISIRAK V,GANGULY D,LEWIS KL,et al.Genetic evidence for the role of plasmacytoid dendritic cells in systemic lupus erythematosus[J].J Exp Med,2014,211(10):1969.
[22]ROWLAND SL,RIGGS JM,GILFILLAN S,et al.Early,transient depletion of plasmacytoid dendritic cells ameliorates autoimmunity in a lupus model[J].J Exp Med,2011,211(10):1977.