Interleukin-13 in asthma pathogenesis.
Bronchial asthma is a complex disorder that is thought to arise as a result of aberrant T-lymphocyte responses to noninfectious environmental antigens. In particular, the symptoms of asthma are closely associated with the presence of activated T-helper 2 cell (Th2) cytokine-producing cells [interleukin (IL)-4, IL-5, IL-9, and IL-13] in the airway wall. Although each of the Th2 cytokines likely contributes to the overall immune response directed against environmental antigens, a substantial body of evidence points to a singular role for IL-13 in the regulation of the allergic diathesis. Initial studies in animal models of disease provided compelling evidence that IL-13, independently of other Th2 cytokines, was both necessary and sufficient to induce all features of allergic asthma. The importance of IL-13 in allergic disorders in humans is supported by consistent associations between tissue IL-13 levels and genetic variants in the IL-13 gene with asthma and related traits. With the preponderance of evidence continuing to support a pivotal role for IL-13 in allergic disorders, attention is now turned toward understanding the mechanisms by which this cytokine may mediate the pathophysiological features of allergic disease. The emerging paradigm is that IL-13 induces features of the allergic response via a complex array of actions on resident airway cells rather than through traditional effector pathways involving eosinophils and immunoglobulin E-mediated events. In light of these recent developments, this review explores our current understanding of the singular role of IL-13 in the pathogenesis of asthma, with a particular focus on new insights into the mechanisms by which IL-13 mediates various features of asthma.
Wills-Karp
Marsha
M
Division of Immunobiology, Children's Hospital Medical Center, Cincinnati, OH 45208, USA. wildc7@chmcc.org
D001249:Asthma / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018793:Interleukin-13 / Q000378:metabolism*; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin / Q000378:metabolism; D053660:Receptors, Interleukin-13; D012137:Respiratory System / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
C508181:IL13RA1 protein, human; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13