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.
Chatila
Talal A
TA
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
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