Abstract
Chemerin, the natural ligand of the ChemR23 receptor, acts as a chemoattractant agent for macrophages, immature dendritic cells, and NK cells. In this study, we investigated the role of the chemerin/ChemR23 system in the physiopathology of inflammatory lung diseases using wild type (WT) and knock-out mice for the receptor (ChemR23-/-). Whereas no differences are observed in models of lung fibrosis and asthma, ChemR23-/- mice present higher mortality and morbidity in a model of viral pneumonia induced by the pneumonia virus of mice (PVM). ChemR23-/- mice display delayed viral clearance, and impaired acquired immunity contrasting with an excessive innate response and recruitment of neutrophils. Lower recruitment of type I interferon-producing plasmacytoid dendritic cells (pDCs) may explain the delayed acquired response and viral clearance in ChemR23-/- mice. However, the stronger inflammation observed in these mice is not due to defective pDC recruitment but rather to the loss of an anti-inflammatory role of chemerin on non-leukocytic cells. Indeed, experiments involving adoptive transfer of pDCs and bone marrow transplantation exclude the role of ChemR23-expressing pDCs and more generally leukocytes in the protection against excessive inflammation. Moreover, a strong anti-inflammatory role of chemerin is observed in a model of acute lung injury induced by instillation of lipopolyssacharide (LPS), which is strictly dependent of ChemR23. Altogether, our data suggest a role of the chemerin/ChemR23 system in the modulation of innate immunity and this is likely mediated by non-leukocytic cells, such as lung endothelial or epithelial cells.
- © 2011 ERS
