Anti-HMGB1 Neutralizing Antibody Ameliorates Neutrophilic Airway Inflammation by Suppressing Dendritic Cell-Mediated Th17 Polarization
We demonstrate that high mobility group box 1 protein (HMGB1) directs Th17 skewing by regulating dendritic cell (DC) function. First, our in vitro studies reveal that recombinant HMGB1 (rHMGB1) activates myeloid DCs to produce IL-23 in vitro, and rHMGB1-activated DCs prime naïve lymphocytes to produ...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/257930 |
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| author | Fang Zhang Gang Huang Bo Hu Li-Ping Fang E-Hong Cao Xiao-Feng Xin Yong Song Yi Shi |
| author_facet | Fang Zhang Gang Huang Bo Hu Li-Ping Fang E-Hong Cao Xiao-Feng Xin Yong Song Yi Shi |
| author_sort | Fang Zhang |
| collection | DOAJ |
| description | We demonstrate that high mobility group box 1 protein (HMGB1) directs Th17 skewing by regulating dendritic cell (DC) function. First, our in vitro studies reveal that recombinant HMGB1 (rHMGB1) activates myeloid DCs to produce IL-23 in vitro, and rHMGB1-activated DCs prime naïve lymphocytes to produce the Th17 cytokine IL-17A. Second, we demonstrate that anti-HMGB1 neutralizing antibody attenuates HMGB1 expression, neutrophilic inflammation, airway hyperresponsiveness, and Th17-related cytokine secretion in vivo by using a murine model of neutrophilic asthma induced by ovalbumin (OVA) plus lipopolysaccharide (LPS). Furthermore, anti-HMGB1 neutralizing antibody decreases the number of Th17 cells in lung cells and suppresses the production of IL-23 by lung CD11C+ APCs. Finally, we show that intranasal adoptive transfer of rHMGB1-activated DCs was sufficient to restore lung neutrophilic inflammation and the Th17 response in a DC-driven model of asthma, whereas the transfer of rHMGB1 plus anti-HMGB1-treated mDCs significantly reduced these inflammation phenotypes. These data suggest, for the first time, that HMGB1 drives the DC-polarized Th17-type response in allergic lung inflammation and that blocking HMGB1 may benefit the attenuation of neutrophilic airway inflammation in asthma. |
| format | Article |
| id | doaj-art-306eb52445be4e57914fed174aefa1c7 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-306eb52445be4e57914fed174aefa1c72025-02-03T01:12:48ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/257930257930Anti-HMGB1 Neutralizing Antibody Ameliorates Neutrophilic Airway Inflammation by Suppressing Dendritic Cell-Mediated Th17 PolarizationFang Zhang0Gang Huang1Bo Hu2Li-Ping Fang3E-Hong Cao4Xiao-Feng Xin5Yong Song6Yi Shi7Department of Pulmonary Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, ChinaDepartment of Medical Genetics, Third Military Medical University, Chongqing 430038, ChinaDepartment of Administration, 105 Hospital, Hefei 230031, ChinaDepartment of Pulmonary Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, ChinaDepartment of Pulmonary Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, ChinaDepartment of Pulmonary Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, ChinaDepartment of Pulmonary Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, ChinaDepartment of Pulmonary Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, ChinaWe demonstrate that high mobility group box 1 protein (HMGB1) directs Th17 skewing by regulating dendritic cell (DC) function. First, our in vitro studies reveal that recombinant HMGB1 (rHMGB1) activates myeloid DCs to produce IL-23 in vitro, and rHMGB1-activated DCs prime naïve lymphocytes to produce the Th17 cytokine IL-17A. Second, we demonstrate that anti-HMGB1 neutralizing antibody attenuates HMGB1 expression, neutrophilic inflammation, airway hyperresponsiveness, and Th17-related cytokine secretion in vivo by using a murine model of neutrophilic asthma induced by ovalbumin (OVA) plus lipopolysaccharide (LPS). Furthermore, anti-HMGB1 neutralizing antibody decreases the number of Th17 cells in lung cells and suppresses the production of IL-23 by lung CD11C+ APCs. Finally, we show that intranasal adoptive transfer of rHMGB1-activated DCs was sufficient to restore lung neutrophilic inflammation and the Th17 response in a DC-driven model of asthma, whereas the transfer of rHMGB1 plus anti-HMGB1-treated mDCs significantly reduced these inflammation phenotypes. These data suggest, for the first time, that HMGB1 drives the DC-polarized Th17-type response in allergic lung inflammation and that blocking HMGB1 may benefit the attenuation of neutrophilic airway inflammation in asthma.http://dx.doi.org/10.1155/2014/257930 |
| spellingShingle | Fang Zhang Gang Huang Bo Hu Li-Ping Fang E-Hong Cao Xiao-Feng Xin Yong Song Yi Shi Anti-HMGB1 Neutralizing Antibody Ameliorates Neutrophilic Airway Inflammation by Suppressing Dendritic Cell-Mediated Th17 Polarization Mediators of Inflammation |
| title | Anti-HMGB1 Neutralizing Antibody Ameliorates Neutrophilic Airway Inflammation by Suppressing Dendritic Cell-Mediated Th17 Polarization |
| title_full | Anti-HMGB1 Neutralizing Antibody Ameliorates Neutrophilic Airway Inflammation by Suppressing Dendritic Cell-Mediated Th17 Polarization |
| title_fullStr | Anti-HMGB1 Neutralizing Antibody Ameliorates Neutrophilic Airway Inflammation by Suppressing Dendritic Cell-Mediated Th17 Polarization |
| title_full_unstemmed | Anti-HMGB1 Neutralizing Antibody Ameliorates Neutrophilic Airway Inflammation by Suppressing Dendritic Cell-Mediated Th17 Polarization |
| title_short | Anti-HMGB1 Neutralizing Antibody Ameliorates Neutrophilic Airway Inflammation by Suppressing Dendritic Cell-Mediated Th17 Polarization |
| title_sort | anti hmgb1 neutralizing antibody ameliorates neutrophilic airway inflammation by suppressing dendritic cell mediated th17 polarization |
| url | http://dx.doi.org/10.1155/2014/257930 |
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