title: High mobility group box 1 protein suppresses T cell-mediated immunity via CD11c(low)CD45RB(high) dendritic cell differentiation.
abstract: OBJECTIVE
  High mobility group box 1 protein (HMGB1) has been identified as a late proinflammatory cytokine and plays a key role in immune regulation. However, it is not yet clear whether HMGB1 can induce the activation and differentiation of dendritic cell (DC) subsets and subsequently modulate immune function of T cells. This study was performed to investigate the effect of HMGB1 on the differentiation of splenic DCs and its influence on T cell-mediated immunity in terms of DC subsets CD11c(low)CD45RB(high) DCs and CD11c(high)CD45RB(low) DCs in male BALB/c mice spleens in vitro.
  
  
  RESULTS
  MACS microbeads were used to isolate splenic DCs, CD11c(low)CD45RB(high) DCs, CD11c(high)CD45RB(low) DCs and CD4(+) T cells. The percentage of CD11c(low)CD45RB(high) DCs was significantly increased after treatment with HMGB1 compared to their counterparts (CD11c(high)CD45RB(low) DCs). It was found that unlike the gradually increasing interleukin (IL)-12 secretion of CD11c(high)CD45RB(low) DCs induced by HMGB1, CD11c(low)CD45RB(high) DCs showed a obvious dose-dependent response between IL-10 production and HMGB1 stimulation. In order to verify whether the alteration of CD4(+) T cells was mainly associated with the differentiation of splenic DCs mediated by HMGB1 to CD11c(low)CD45RB(high) DCs, anti-IL-12 receptor (IL-12R) or anti-IL-10R monoclonal antibody was used to inhibit the effect of CD11c(high)CD45RB(low) DCs or CD11c(low)CD45RB(high) DCs in CD4(+) T cells mixed lymphocyte reaction culture. After treatment with anti-IL-12R or anti-IL-10 monoclonal antibody in CD4(+) T cells+CD11c(high)CD45RB(low) DCs or CD11c(low)CD45RB(high) DCs mixed lymphocyte reaction, the induction of these DCs on T cells was inhibited dramatically.
  
  
  CONCLUSIONS
  These data demonstrated that HMGB1 might induce the differentiation of splenic DCs to CD11c(low)CD45RB(high) DCs followed by shifting of Th1 to Th2 with enhancement of T lymphocyte immune function in vitro. Also, the effect of HMGB1 on T cell differentiation to Th2 was not associated with the inhibition of IL-12 production in CD11c(high)CD45RB(low) DCs.
authors.affiliation: Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, PR China.
authors.forename: Qing-yang
authors.initials: QY
authors.lastname: Liu
authors.forename: Yong-ming
authors.initials: YM
authors.lastname: Yao
authors.forename: Yong-hong
authors.initials: YH
authors.lastname: Yan
authors.forename: Ning
authors.initials: N
authors.lastname: Dong
authors.forename: Zhi-yong
authors.initials: ZY
authors.lastname: Sheng
mesh_terms: D000818:Animals; D039521:CD11c Antigen / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D024243:HMGB1 Protein / Q000502:physiology*; D007111:Immunity, Cellular / Q000502:physiology*; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D039521:CD11c Antigen; D024243:HMGB1 Protein; D017493:Leukocyte Common Antigens