Functional study of immature dendritic cells co-transfected with IL-10 and TGF-beta 1 genes in vitro

被引:34
作者
Chen, Lihong [1 ]
Qiu, Minglian [2 ]
He, Wubing [3 ]
Huang, Aimin [1 ]
Liu, Jingfeng [4 ]
机构
[1] Fujian Med Univ, Dept Pathol, Fuzhou 350004, Fujian, Peoples R China
[2] Fujian Med Univ, Div Thorac Surg, Affiliated Hosp 1, Fuzhou 350004, Fujian, Peoples R China
[3] Fujian Med Univ, Shengli Clin Med Coll, Fuzhou 350004, Fujian, Peoples R China
[4] Fujian Med Univ, Div Hepatobiliary Surg, Hepat Dis Ctr, Affiliated Hosp 1, Fuzhou 350005, Fujian, Peoples R China
关键词
Dendritic cells; Transforming growth factor-beta1; Interleukin-10; Immune tolerance; REGULATORY T-CELLS; GROWTH-FACTOR-BETA; TGF-BETA; ANTIGEN; IMMUNOSUPPRESSION; DYSFUNCTION; EXPRESSION; GENERATION; TOLERANCE; THERAPY;
D O I
10.1007/s11033-012-1468-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Dendritic cells (DC) have important functions in T cell immunity and T cell tolerance. Previous studies suggest that immature dendritic cells (imDCs) might be involved in the induction of peripheral T cell tolerance. While interleukin-10 (IL-10) functions at different levels of the immune response, transforming growth factor-beta 1 (TGF-beta 1) is considered to be a key factor in immune tolerance. In this study, we investigated the effects of immature DC (imDC) co-transfected with IL-10 and TGF-beta 1 genes (IL-10-TGF-beta 1-imDC) on inducing immune tolerance. Moreover, we compared the effects of IL-10-TGF-beta 1-imDC with IL-10 transfected imDC (IL-10-imDC) and TGF-beta 1-transfected imDC (TGF-beta 1-imDC), respectively. IL-10-TGF-beta 1-imDC resulted in the down-regulation of MHC class II, CD80 and CD86. IL-10-TGF-beta 1-imDC could induce T cell hyporesponsiveness, and was reluctant to proliferate. IL-10-TGF-beta 1-imDC was more effective than IL-10-imDC and TGF-beta 1-imDC, respectively. In summary, co-expression of IL-10 and TGF-beta 1 affected the immunity of imDCs and enhanced their tolerogenicity. It might be a promising therapy for donor-specific tolerance after organ transplantation.
引用
收藏
页码:6633 / 6639
页数:7
相关论文
共 26 条
[1]
Distinct contributions of TNF and LT cytokines to the development of dendritic cells in vitro and their recruitment in vivo [J].
Abe, K ;
Yarovinsky, FO ;
Murakami, T ;
Shakhov, AN ;
Tumanov, AV ;
Ito, D ;
Drutskaya, LN ;
Pfeffer, K ;
Kuprash, DV ;
Komschlies, KL ;
Nedospasov, SA .
BLOOD, 2003, 101 (04) :1477-1483
[2]
Abediankenari S, 2009, IRAN J ALLERGY ASTHM, V8, P25, DOI 08.01/ijaai.2530
[3]
Toll-like receptor 4-dependent activation of dendritic cells by β-defensin 2 [J].
Biragyn, A ;
Ruffini, PA ;
Leifer, CA ;
Klyushnenkova, E ;
Shakhov, A ;
Chertov, O ;
Shirakawa, AK ;
Farber, JM ;
Segal, DM ;
Oppenheim, JJ ;
Kwak, LW .
SCIENCE, 2002, 298 (5595) :1025-1029
[4]
TGF-β1 gene-modified, immature dendritic cells delay the development of inflammatory bowel disease by inducing CD4+Foxp3+ regulatory T cells [J].
Cai, Zhijian ;
Zhang, Wei ;
Li, Min ;
Yue, Yinpu ;
Yang, Fei ;
Yu, Lei ;
Cao, Xuetao ;
Wang, Jianli .
CELLULAR & MOLECULAR IMMUNOLOGY, 2010, 7 (01) :35-43
[5]
Immunosuppression induced by immature dendritic cells is mediated by TGF-β/IL-10 double-positive CD4+ regulatory T cells [J].
Cools, N. ;
Van Tendeloo, V. F. I. ;
Smits, E. L. J. M. ;
Lenjou, M. ;
Nijs, G. ;
Van Bockstaele, D. R. ;
Berneman, Z. N. ;
Ponsaerts, P. .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2008, 12 (02) :690-700
[6]
Immunosuppressive strategies in transplantation [J].
Denton, MD ;
Magee, CC ;
Sayegh, MH .
LANCET, 1999, 353 (9158) :1083-1091
[7]
Genealogy, expression, and cellular function of transforming growth factor-β [J].
Govinden, R ;
Bhoola, KD .
PHARMACOLOGY & THERAPEUTICS, 2003, 98 (02) :257-265
[8]
Dendritic cells as immune regulators: the mouse model [J].
Griffiths, K. L. ;
O'Neill, H. C. .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2008, 12 (5B) :1909-1914
[9]
Gene therapy-mediated CD40L and CD28 co-stimulatory signaling blockade plus transient anti-xenograft antibody suppression induces long-term acceptance of cardiac xenografts [J].
Hua, N ;
Yamashita, K ;
Hashimoto, T ;
Masunaga, T ;
Fujita, M ;
Furukawa, H ;
Uede, T ;
Todo, S .
TRANSPLANTATION, 2004, 78 (10) :1463-1470
[10]
TGF-β Is Required To Maintain the Pool of Immature Langerhans Cells in the Epidermis [J].
Kel, Junda M. ;
Girard-Madoux, Mathilde J. H. ;
Reizis, Boris ;
Clausen, Bjorn E. .
JOURNAL OF IMMUNOLOGY, 2010, 185 (06) :3248-3255