title: A protective role for C5a in the development of allergic asthma associated with altered levels of B7-H1 and B7-DC on plasmacytoid dendritic cells.
abstract: The role of complement in the development of maladaptive immunity in experimental allergic asthma is unclear. In this study, we show that C3a receptor (C3aR)-deficient mice are protected from the development of Th2 immunity in a model of house dust mite-induced asthma. C5a receptor (C5aR)-targeting of C3aR-deficient mice during allergen sensitization not only reversed the protective effect but enhanced Th2 cytokine production, airway inflammation, and airway responsiveness, suggesting that the reduced allergic phenotype in C3aR-deficient mice results from protective C5aR signaling. In support of this view, C5aR expression in C3aR-deficient pulmonary dendritic cells (DCs) was increased when compared with wild-type DCs. Moreover, C5aR targeting regulated the frequency of pulmonary plasmacytoid DCs expressing costimulatory molecules B7-H1 and B7-DC. Ex vivo targeting of B7-H1 and B7-DC increased Th2 cytokine production from T cells of wild-type but not of C5aR-targeted mice, suggesting a protective role for C5a through regulation of B7 molecule expression on plasmacytoid DCs.
authors.affiliation: Division of Molecular Immunology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
authors.forename: Xun
authors.initials: X
authors.lastname: Zhang
authors.forename: Ian P
authors.initials: IP
authors.lastname: Lewkowich
authors.forename: Gabriele
authors.initials: G
authors.lastname: Köhl
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Clark
authors.forename: Marsha
authors.initials: M
authors.lastname: Wills-Karp
authors.forename: Jörg
authors.initials: J
authors.lastname: Köhl