High mobility group box 1 protein suppresses T cell-mediated immunity via CD11clowCD45RBhigh dendritic cell differentiation

Abstract

AimHigh 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 CD11clowCD45RBhigh DCs and CD11chighCD45RBlow DCs in male BALB/c mice spleens in vitro. ResultsMACS microbeads were used to isolate splenic DCs, CD11clowCD45RBhigh DCs, CD11chighCD45RBlow DCs and CD4+ T cells. The percentage of CD11clowCD45RBhigh DCs was significantly increased after treatment with HMGB1 compared to their counterparts (CD11chighCD45RBlow DCs). It was found that unlike the gradually increasing interleukin (IL)-12 secretion of CD11chighCD45RBlow DCs induced by HMGB1, CD11clowCD45RBhigh 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 CD11clowCD45RBhigh DCs, anti-IL-12 receptor (IL-12R) or anti-IL-10R monoclonal antibody was used to inhibit the effect of CD11chighCD45RBlow DCs or CD11clowCD45RBhigh 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+CD11chighCD45RBlow DCs or CD11clowCD45RBhigh DCs mixed lymphocyte reaction, the induction of these DCs on T cells was inhibited dramatically. ConclusionThese data demonstrated that HMGB1 might induce the differentiation of splenic DCs to CD11clowCD45RBhigh 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 CD11chighCD45RBlow DCs.