title: [Rapamycin-conditioned dendritic cells induced immune tolerance through the regulation of Treg/Th17 cells in mice].
abstract: OBJECTIVE
  To investigate the effect of tolerogenic dendritic cells (Tol-DC) generated by Rapamycin (Rapa) on the differentiation of Treg/Th17 cells and explore the possible mechanism of tolerance induction.
  
  
  METHODS
  DC progenitors from mouse bone marrow were propagated with granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin (IL)-4 stimulation for 6 days in the presence or absence of Rapa (20 ng/ml). During DC culture, morphology of cell was observed under electron microscope. Cell surface expression of CD11c, CD40 and CD80 was analyzed by flow cytometry. The antigen-presenting function of DC was determined by one-way mixed leukocyte reactions. In vivo, the recipient BALB/c mice receiving transplantation of skin allograft from C57BL/6 mice were divided into control, Rapa, immature DC (imDC) and Tol-DC group. The survival time of the skin allograft was observed and Treg/Th17 cells were analyzed by flow cytometry in each group.
  
  
  RESULTS
  The immunephenotypic analysis showed that in comparison with those in the control group and the LPS group the expression of the co-stimulatory molecules CD40 and CD80 were significantly lower in the Rapa-group and Rapa+LPS group. The ability to stimulate proliferation of T cells of the same genotype in the Rapa-group was significantly inhibited (P<0.01). In the in vivo experiment, the mice's survival time remarkably prolonged, the percentage of Treg cells was enhanced and Th17 cells was reduced in the mice's spleen in Tol-DC group.
  
  
  CONCLUSIONS
  Tol-DC generated by Rapamycin can significantly induce immune tolerance through up-regulate Tregs and down-regulate Th17 cells. The present study highlights the therapeutic potential of preventing allograft rejection using in vitro-generated Tol-DCs, which can be loaded with donor antigen, and potentially used to promote organ transplant tolerance.
authors.affiliation: Department of Urology, Chaoyang Hospital, the Capital Medical University, Beijing 100020, China.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Urology, Chaoyang Hospital, the Capital Medical University, Beijing 100020, China.
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Department of Urology, Chaoyang Hospital, the Capital Medical University, Beijing 100020, China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Urology, Chaoyang Hospital, the Capital Medical University, Beijing 100020, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Urology, Chaoyang Hospital, the Capital Medical University, Beijing 100020, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Urology, Chaoyang Hospital, the Capital Medical University, Beijing 100020, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of Urology, Chaoyang Hospital, the Capital Medical University, Beijing 100020, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Urology, Chaoyang Hospital, the Capital Medical University, Beijing 100020, China; Email: zxd581@263.net.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D019013:CD40 Antigens; D003713:Dendritic Cells; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020123:Sirolimus; D050378:T-Lymphocytes, Regulatory; D058504:Th17 Cells
chemical_list: D019013:CD40 Antigens; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020123:Sirolimus