title: Recombinant HMGB1 A box protein inhibits Th17 responses in mice with neutrophilic asthma by suppressing dendritic cell-mediated Th17 polarization.
abstract: High mobility group box chromosomal protein 1 (HMGB1) is a critical pro-inflammatory cytokine involved in diverse inflammatory diseases and has important immunomodulatory effects on allergic asthma. Our recent studies demonstrate that HMGB1) ^ReloadFigure=Yes1 expression increases in the lung tissue and associates with interleukin-17(+) (IL-17) helper T cell (Th17) responses in a murine model of neutrophilic asthma. In this study, to examine the immunomodulatory mechanisms of HMGB1, we evaluated the effects of recombinant HMGB1 A box (an antagonist of HMGB1) administration on allergic airway inflammation and lung antigen-presenting cell (APC) function in a murine model of neutrophilic asthma. In OVA-challenged mice, rHMGB1 A box attenuated HMGB1 expression, airway neutrophilic inflammation and hyper-responsiveness. In addition, the administration of rHMGB1 A box decreased the number of Th17 cells and IL-23(+) CD11c(+) APCs in lung cells. In vivo, rHMGB1 A box revealed an inhibitory effect of rHMGB1-activated dendritic cells (DCs) to produce IL-23 and induce a Th17 response. Finally, we showed that adoptive transfer of rHMGB1-activated DCs was sufficient to restore the characteristics of neutrophilic asthma in a DCs-driven model of asthma, whereas the transfer of rHMGB1 A box plus rHMGB1-activated DCs significantly reduced these inflammation phenotypes. These data demonstrate that rHMGB1 A box may have therapeutic effects on controlling Th17 polarization and airway inflammation in neutrophilic asthma by blocking the HMGB1 pathway on DCs.
authors.affiliation: Department of Pulmonary Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China. Electronic address: zhangfanglab@163.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Medical Genetics, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Pulmonary Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Pulmonary Medicine, Xinqiao Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Gui-sheng
authors.initials: GS
authors.lastname: Qian
authors.affiliation: Department of Pulmonary Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China. Electronic address: yong_song6310@yahoo.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Song
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D018845:CD11 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D011994:Recombinant Proteins / Q000627:therapeutic use; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D018845:CD11 Antigens; D024243:HMGB1 Protein; D020381:Interleukin-17; D053759:Interleukin-23; D011994:Recombinant Proteins
keywords: Dendritic cell; HMGB1; Neutrophilic asthma; Th17