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Mediators of Inflammation
Volume 2014, Article ID 257930, 11 pages
http://dx.doi.org/10.1155/2014/257930
Research Article

Anti-HMGB1 Neutralizing Antibody Ameliorates Neutrophilic Airway Inflammation by Suppressing Dendritic Cell-Mediated Th17 Polarization

1Department of Pulmonary Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China
2Department of Medical Genetics, Third Military Medical University, Chongqing 430038, China
3Department of Administration, 105 Hospital, Hefei 230031, China

Received 17 January 2014; Revised 3 April 2014; Accepted 3 April 2014; Published 15 May 2014

Academic Editor: Anshu Agrawal

Copyright © 2014 Fang Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.