HMGB1 Preferentially Induces Th2 Polarization And Response In Allergic Asthma

Objective: High Mobility Group Box 1(HMGB1)is a common inflammatory mediator that has an increase level in peripheral blood of asthmatic patients.HMGB1 could shift the human Th1/Th2 balance into Th2 in vitro.Thus,in the present study,we investigate the role of HMGB1 in the Th2-type response of allergic asthma.Methods: Induction of allergic asthma in mice.After exogenous HMGB1 and/or anti-HMGB1 administration,histological analysis,cytological analysis and ELISA assay were performed to explore the e ffect of HMGB1 in acute allergic asthma.Th2 and Th1 percentages were analyzed after exogenous HMGB1 injection.The splenic CD4+ T cells from mice with allergic asthma were isolated and stimulated by IL-4 or IL-12 to differentiate into Th2 or Th1 cells,respectively.Meanwhile,both Th2 and Th1 cells were stimulated by HMGB1 in the presence of HMGB1 neutralizing antibody.Finally,the percentage of Th2 and Th1 cells,the expression levels for GATA3 and T-bet,and the levels for IL-4 and IFN-? in the supernatant of culture media were assessed.Results: In vivo,HMGB1 could increase Th2 percentage but reduce Th1 in asthmatic mice.Consistently,the percentage of Th2 in vitro was increased and Th1 was decreased after addition of exogenous HMGB1.In addition,both GATA3 and IL-4 levels were increased after addition of HMGB1,while the expression of T-bet and IFN-? level was decreased.All these effects could be reversed by the HMGB1 neutralizing antibody.Conclusions: HMGB1 could induce Th2 polarization and response but suppress Th1 activation in allergic asthma both in vivo and in vitro,which would provide a novel insight into the pathogenesis and therapeutic study of allergic asthma.