Article abstract
Nature Medicine 13, 570 - 578 (2007)
Published online: 15 April 2007 | doi:10.1038/nm1580
Osteopontin has a crucial role in allergic airway disease through regulation of dendritic cell subsets
Georgina Xanthou1, Themis Alissafi1, Maria Semitekolou1, Davina C M Simoes2, Erasmia Economidou3, Mina Gaga3, Bart N Lambrecht4, Clare M Lloyd5 & Vily Panoutsakopoulou1
Abstract
Osteopontin (Opn) is important for T helper type 1 (TH1) immunity and autoimmunity. However, the role of this cytokine in TH2-mediated allergic disease as well as its effects on primary versus secondary antigenic encounters remain unclear. Here we demonstrate that OPN is expressed in the lungs of asthmatic individuals and that Opn-s, the secreted form of Opn, exerts opposing effects on mouse TH2 effector responses and subsequent allergic airway disease: pro-inflammatory at primary systemic sensitization, and anti-inflammatory during secondary pulmonary antigenic challenge. These effects of Opn-s are mainly mediated by the regulation of TH2-suppressing plasmacytoid dendritic cells (DCs) during primary sensitization and TH2-promoting conventional DCs during secondary antigenic challenge. Therapeutic administration of recombinant Opn during pulmonary secondary antigenic challenge decreased established TH2 responses and protected mice from allergic disease. These effects on TH2 allergic responses suggest that Opn-s is an important therapeutic target and provide new insight into its role in immunity.
- Cellular Immunology Laboratory, Division of Cell Biology, Center for Basic Research, Foundation for Biomedical Research of the Academy of Athens, 4 Soranou Efessiou Street, 115 27 Athens, Greece.
- M. Simou and G.P. Livanos Laboratories, Department of Critical Care and Pulmonary Medicine, National and Kapodistrian University of Athens, School of Medicine, 3 Ploutarchou Street, 106 75 Athens, Greece.
- Asthma Center and 7th Respiratory Medicine Department, Sotiria Athens Chest Hospital, 152 Mesogion Avenue, 115 27 Athens, Greece.
- Department of Pulmonary Medicine, Erasmus University Medical Center, 50 Molewaterplein Drive, 3015 GE Rotterdam, The Netherlands.
- Leukocyte Biology Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College, Exhibition Road, SW7 2AZ London, UK.
Correspondence to: Vily Panoutsakopoulou1 e-mail: vpan@bioacademy.gr
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