title: Dendritic cells play an essential role in transplantation responses via myeloid differentiation factor 88 signaling.
abstract: BACKGROUND
  DCs (dendritic cells), play an important role in allo-recognition, but there is no direct evidence that DCs trigger and control allo-responses. In this study, we investigated the role of DCs by using a self-created MyD88 (myeloid differentiation factor 88) inhibitor and a minor antigen-mismatched (HY-mismatched) skin transplantation model in mice.
  
  
  METHODS
  An HY-mismatched skin allograft model (BALB/c ♂ → BALB/c ♀) using MyD88-knockout mice was employed in this study. WT (Wild-type) BALB/c immature BMDCs (bone marrow dendritic cells) were co-cultured with or without TJ-M2010 in vitro for 12 hours before transfusion of DCs (2× 10(7)/mouse) into recipients of skin transplantations. Wild-type BALB/c BMDCs were stimulated by the TLR9 (Toll-like receptor 9) agonist, CpG (cytidine-phosphate-guanosine), in the presence of TJ-M2010 or not for 12 hours in vitro. Costimulatory molecules CD80/CD86 were analyzed by flow cytometry. WT C57BL/6 naïve T cells stained with CFSE (carboxyfluorescein diacetate succinimidyl ester) were co-cultured with WT BALB/c DCs for 3 days in the presence or absence of TJ-M2010. CD3(+)/CFSE(+) cells were analyzed by flow cytometry.
  
  
  RESULTS
  TJ-M2010 inhibited DC maturation and T cell proliferation. Permanent survival of the skin allografts was observed in MyD88 knockout (MyD88- KO) mice. However, skin allografts were rejected by MyD88-KO mice infused with wild-type (WT) DCs. More interestingly, after treating the WT DCs with TJ-M2010, the DC infusion could not reverse the tolerance to skin allografts.
  
  
  CONCLUSIONS
  This study provided evidence that DCs play an essential role in alloresponses.
authors.affiliation: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, Key Laboratory of Organ Transplantation, Ministry of Public Health, Wuhan, China.
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: T
authors.initials: T
authors.lastname: Yang
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: F
authors.initials: F
authors.lastname: Jiang
authors.forename: W
authors.initials: W
authors.lastname: Huang
authors.forename: P
authors.initials: P
authors.lastname: Zhou
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D015398:Signal Transduction; D016038:Skin Transplantation
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88