International immunopharmacology, 2015-01, Vol.24 (1), p.110-118
2015
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- Autor(en) / Beteiligte
- Titel
- Recombinant HMGB1 A box protein inhibits Th17 responses in mice with neutrophilic asthma by suppressing dendritic cell-mediated Th17 polarization
- Ist Teil von
- International immunopharmacology, 2015-01, Vol.24 (1), p.110-118
- Ort / Verlag
- Netherlands: Elsevier B.V
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. •HMGB1 A box prevents airway inflammation in neutrophilic asthma.•HMGB1 plays an important role in Th17 polarization of neutrophilic asthma.•HMGB1 A box inhibits Th17 polarization by blocking HMGB1 signaling on DCs.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1567-5769eISSN: 1878-1705DOI: 10.1016/j.intimp.2014.11.005Titel-ID: cdi_proquest_miscellaneous_1660391335
- Format
- –
- Schlagworte
- Adoptive Transfer, Animals, Antigen-Presenting Cells - drug effects, Antigen-Presenting Cells - immunology, Asthma - drug therapy, Asthma - immunology, CD11 Antigens - metabolism, Cell Differentiation - drug effects, Cell Movement - drug effects, Cells, Cultured, Dendritic cell, Dendritic Cells - immunology, Disease Models, Animal, Female, Gene Expression Regulation - drug effects, HMGB1, HMGB1 Protein - antagonists & inhibitors, HMGB1 Protein - therapeutic use, Humans, Interleukin-17 - metabolism, Interleukin-23 - metabolism, Mice, Mice, Inbred C57BL, Neutrophilic asthma, Neutrophils - drug effects, Neutrophils - immunology, Recombinant Proteins - therapeutic use, Th17, Th17 Cells - drug effects, Th17 Cells - immunology