Interleukin-4 receptor signaling pathways in asthma pathogenesis.
Asthma is a chronic allergic inflammatory disease, the initiation and progression of which is dependent on the cytokines interleukin (IL)-4 and IL-13 acting through related receptor complexes. Disease pathogenesis is effected by intracellular signaling pathways that couple primarily to specific motifs within the intracellular domain of the IL-4 receptor alpha chain (IL-4Ralpha), a subunit that is common to the IL-4 and IL-13 receptor complexes. Recent studies using genetic approaches have identified distinct functions for the respective IL-4Ralpha-coupled signaling pathways in regulating both early and chronic stages of asthma. Polymorphisms in components of the IL-4 and IL-13 cytokine-receptor axes are associated with allergy and asthma, suggesting that variations among individuals in the activity of this pathway contribute to disease susceptibility and manifestations.
Department of Pediatrics, The David Geffen School of Medicine at the University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-1752, USA. Tchatila@mednet.ucla.edu
Talal A
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Chatila
D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D053662:Interleukin-4 Receptor alpha Subunit; D051379:Mice; D008958:Models, Molecular; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D050800:STAT6 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; C504000:IL4R protein, human; C504002:Il4ra protein, mouse; D018793:Interleukin-13; D053662:Interleukin-4 Receptor alpha Subunit; D011956:Receptors, Cell Surface; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators