Cutting edge: The absence of C3 demonstrates a role for complement in Th2 effector functions in a murine model of pulmonary allergy

Asthma is a chronic disease of the lung resulting from airway obstruction. Although the initiating causes are not entirely clear, the airway inflammat ion in asthma is associated with Th2 lymphocytes and their cytokines, parti cularly IL-4, which play a prominent role in this disease by regulating air way hyperresponsiveness, cosinophil activation, and IgE synthesis. Historic ally, complement was not thought to contribute to the pathogenesis of asthm a. However, using C3-deficient mice in an allergen-induced model of pulmona ry allergy, we demonstrate that complement may impact key features of this disease. When challenged with allergen, mice deficient in C3 exhibit dimini shed airway hyperresponsiveness and lung eosinophilia. Furthermore, these m ice also have dramatically reduced numbers of IL-4-producing cells and atte nuated Ag-specific IgE and IgG1 responses. Collectively, these results demo nstrate that C3-deficient mice have significantly altered allergic lung res ponses and indicate a role for the complement system in promoting Th2 effec tor functions in asthma.