title: Complement activation pathways: a bridge between innate and adaptive immune responses in asthma.
abstract: Although it is widely accepted that allergic asthma is driven by T helper type 2 (Th2)-polarized immune responses to innocuous environmental allergens, the mechanisms driving these aberrant immune responses remain elusive. Recent recognition of the importance of innate immune pathways in regulating adaptive immune responses have fueled investigation into the role of innate immune pathways in the pathogenesis of asthma. The phylogenetically ancient innate immune system, the complement system, is no exception. The emerging paradigm is that C3a production at the airway surface serves as a common pathway for the induction of Th2-mediated inflammatory responses to a variety of environmental triggers of asthma (i.e., allergens, pollutants, viral infections, cigarette smoke). In contrast, C5a plays a dual immunoregulatory role by protecting against the initial development of a Th2-polarized adaptive immune response via its ability to induce tolerogenic dendritic cell subsets. On the other hand, C5a drives type 2-mediated inflammatory responses once inflammation ensues. Thus, alterations in the balance of generation of the various components of the complement pathway either due to environmental exposure changes or genetic alterations in genes of the complement cascade may underlie the recent rise in asthma prevalence in westernized countries.
authors.affiliation: Division of Immunobiology,Center for Immunological Research, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio 45229, USA. wildc7@cchmc.org
authors.forename: Marsha
authors.initials: M
authors.lastname: Wills-Karp
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D003167:Complement Activation / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D018418:Th2 Cells / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D051193:Toll-Like Receptors