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融合蛋白mTSLPR-Ig体外抑制TSLP对树突状细胞的活化 被引量:4

Fusion protein of thymic stromal lymphopoietin-immunoglobulin inhibits the in vitro activation on dendritic cells by TSLP
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摘要 胸腺基质淋巴细胞生成素(thymic stromal lymphopoietin,TSLP)通过结合树突状细胞(dendritic cell,DC)表面TSLP受体(TSLPR)活化DC,在导致哮喘Th1/Th2失衡中发挥重要作用。本研究探讨TSLPR可溶性受体mTSLPR-Ig(小鼠TSLPR胞外段与小鼠Ig Fc段的融合蛋白)体外抑制TSLP活化DC的可行性。实验包括分离培养及鉴定小鼠髓系DC;在TSLP作用DC(TSLP-DC)培养体系中加入mTSLPR-Ig,通过FCM检测mTSLPR-Ig对TSLP-DC表面共刺激分子CD80、CD86、CD40表达的影响;将TSLP、抗原OVA脉冲处理的DC以及DO11.10小鼠脾脏CD4+T细胞在体外共培养,MTT法检测体系中加入mTSLPR-Ig对CD4+T细胞增殖能力的影响,同时ELISA法检测上清中细胞因子IL-4、IL-5、IFN-γ以及IL-10表达水平的变化。结果表明,融合蛋白mTSLPR-Ig显著抑制TSLP-DC表面共刺激分子CD80、CD86、CD40的表达;mTSLPR-Ig体外显著抑制TSLP-DC对抗原特异性T细胞的增殖效应,促进上清中IL-10、IFN-γ表达水平,同时抑制IL-4、IL-5表达水平。mTSLPR-Ig通过抑制TSLP-DC活化及所致的Th2偏移,该融合蛋白有望在哮喘或变应性皮炎等TSLP相关性疾病的治疗中发挥重要作用。 Thymic stromal lymphopoietin(TSLP) can activate dendritic cells(DC) through the combination with TSLP receptor(TSLPR) on DC surface,resulting in Th1/Th2 imbalance in asthma.The aim of this study is to find out the feasibility of the soluble TSLPR receptor(mTSLPR-Ig),constituted by the fusion protein of the extracellular segment of mouse TSLPR and Fc segment of mouse immunoglobulin,to inhibit the activation of DC by TSLP in vitro.The murine myeloid DCs were isolated and identified,and then mTSLPR-IG was added to the culture system,in which DCs were effected byTSLP(TSLP-DCs).The influence of mTSLP-Ig on the expression of surface co-stimulatory molecules CD80,CD86 and CD40 was analyzed by FCM.In addition.the impact of the added mTSLPR-Ig fusion protein on the proliferative activity of CD4+ cells was analyzed by FCM and the changes of cytokine,such as IL-4,IL-5,IFN-γ and IL-10,in the cultural supernatants were detected by ELISA.It was demonstrated that expressions of surface co-stimulatory molecules CD80,CD86 and CD40 were significantly inhibited by fusion protein mTSLPR-Ig and mTSLPR-Ig also could inhibit significantly the proliferative activity of the antigen-specific T cells induced by this fusion protein,and promote the secretion of IL-10 and IFN-γ in the cultural supernatants,but inhibit the expression levels of IL-4 and IL-5.From these observation,it is evident that fusion protein mTSLPR-Ig can inhibit the activation of the TSLP-DCs,resulting Th2 biasis,and it is expected that this protein may play some role in the treatment of the TSLP-related disorders,such as asthma or allergic dermatitis.
出处 《现代免疫学》 CAS CSCD 北大核心 2010年第5期379-383,共5页 Current Immunology
基金 中国博士后科学基金资助项目(20070411050) 江苏省博士后科研资助计划项目(0701023B)
关键词 TSLPR 树突状细胞 TSLP 哮喘 TSLPR dendritic cells TSLP asthma
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  • 1顾春瑜,郑磊,王前.树突状细胞治疗自身免疫性疾病的机制及应用研究进展[J].现代免疫学,2005,25(3):253-255. 被引量:8
  • 2Abe M,Thomson AW.Influence of immunosuppressive drugs on dendritic cells[J].Transplant Immunol,2003,11:357-365.
  • 3Yang J,Bernier SM,Ichim TE,et al.LF15-0195 generates tolerogenic dendritic cells by suppression of NF-kappaB signaling through inhibition of IKK activity[J].J Leukoc Biol.2003,74(3):438-447.
  • 4Min WP,Zhou D,Ichim TE,et al.Inhibitory fccdback loop between tolerogenic dendritic cells and regulatory T cells in transplant tolerance[J].J Immunol,2003,170:1304-1312.
  • 5Bonham CA,Peng LS,Liang XY,et al.Marked prolongation of cardiac allograft survival by dendritic cells genetically engineered with NF-κB oligodeoxyribonucleotide decoys and adenoviral vectors encoding CTLA4-Ig[J].J Immunol,2002,169:3382-3391.
  • 6Ma L,Qian S,Liang X,et al.Prevention of diabetes in NOD mice by administration of dendritic cells deficient in nuclear transcription factor-κB activity[J].Diabetes,2003,52:1976-1985.
  • 7Laderach D,Compagno D,Danos O,et al.RNA interference shows critical requirement for NF-kappaB p50 in the production of IL-12 by human dendritic cells[J].J Immunol,2003,171(4):1750-1757.
  • 8Rohn TA,Boes M,Wohers D,et al.Upregulation of the CLIP self peptide on mature dendritic cells antagonizes T helper type 1 polarization[J].Nat Immunol,2004,5 (9):909-918.
  • 9De Paz HA,Oluwole OO,Adeyeri AO,et al.Immaturerat myeloid dendritic cells generated in low-dose granulocyte macrophage-colony stimulating factor prolong donor-specific rat cardiac allograft survival[J].Transplantation,2003,75(4):521-528.
  • 10Min WP,Gorczynski R,Huang XY,et al.Dendritic cells genetically engineered to express Fas ligand induce donor-specific hyporesponsiveness and prolong allograft survival[J].Jlmmunol,2000,164(1):161-167.

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  • 1赵丽华,任亚娜,聂晓绚,杨洁,高跞,刘袁媛,郭芳,范华骅.调节性DC分泌的外体诱导免疫耐受功能的体外研究[J].现代免疫学,2008,28(1):51-56. 被引量:4
  • 2叶乐平,李昌崇,李绍波,范小芳,胡晓光,张维溪,李孟荣.信号转导子和转录激活子6及其mRNA在哮喘大鼠气道炎症中的作用[J].中国病理生理杂志,2006,22(1):107-111. 被引量:5
  • 3Jaen O, Rulle S, Bessis N, et al. Dendritic cells modulated by innate immunity improve collagen-induced arthritis and induce regulatory T cells in vivo[J]. Immunology, 2009, 126: 35-44.
  • 4Ying S, O'Connor B, Ratoff J, et al. Expression and cellular provenance of thymic stromal lymphopoietin and chemokines in patients with severe asthma and chronic obstructive pul monary disease[J]. J Immunol, 2008, 181:2790-2798.
  • 5Zhou B, Headley MB, Aye T, et al. Reversal of thymic stromal lymphopoietin-induced airway inflammation through inhibition of Th2 responses[J]. J Immunol, 2008, 181: 6557- 6562.
  • 6Wegmann M. Th2 cells as targets for therapeutic intervention in allergic bronchial asthma [J]. Expert Rev Mol Diagn, 2009, 9: 85-100.
  • 7A1 Shami A, Spolski R, Kelly J, et al. A role for TSLP in the development of inflammation in an asthma model[J]. J Exp Med, 2005, 202:829-839.
  • 8Zhou B, Comeau MR, De Smedt T, et al. Thymic stromal lymphopoietin as a key initiator of allergic airway inflamma tion in mice[J]. Nat Immunol, 2005, 6: 1047-1053.
  • 9Shi L, Leu SW, Xu F, etal. Local blockade of TSLP reeeptor alleviated allergic disease by regulating airway dendritic cells[J]. Clin Immunol, 2008, 129: 202-210.
  • 10Sims JE, Williams DE, Morrissey PJ, et al. Molecular cloning and biological characterization of a novel murine lymphoid growth factor[J]. J Exp Med, 2000, 192: 671-680.

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