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Targeted Inactivation of the IL-4 Receptor α Chain I4R Motif Promotes Allergic Airway Inflammation
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 2003
- Publisher :
- Rockefeller University Press, 2003.
-
Abstract
- The insulin/interleukin-4 (IL-4) receptor (I4R) motif mediates the association of insulin receptor substrate (IRS)-2 with the interleukin-4 (IL-4)Rα chain and transduces mitogenic signals in response to IL-4. Its physiological functions were analyzed in mice with a germline point mutation that changed the motif's effector tyrosine residue into phenylalanine (Y500F). The Y500F mutation abrogated IRS-2 phosphorylation and impaired IL-4–induced CD4+ T lymphocyte proliferation but left unperturbed Stat6 activation, up-regulation of IL-4-responsive gene products, and Th cell differentiation under Th2 polarizing conditions. However, in vivo the Y500F mutation was associated with increased allergen-induced IgE production, airway responsiveness, tissue eosinophilia, and mucus production. These results define an important role for the I4R motif in regulating allergic inflammation.
- Subjects :
- Insulin Receptor Substrate Proteins
Immunology
Biology
Article
interleukin 4 receptor
Allergic inflammation
Mice
03 medical and health sciences
Th2 Cells
0302 clinical medicine
Insulin receptor substrate
Interleukin-4 receptor
Respiratory Hypersensitivity
insulin receptor substrate
Animals
Immunology and Allergy
Tyrosine
Receptor
030304 developmental biology
Inflammation
0303 health sciences
targeted mutagenesis
Point mutation
Intracellular Signaling Peptides and Proteins
Immunoglobulin E
asthma
Phosphoproteins
Molecular biology
Receptor, Insulin
Receptors, Interleukin-4
Mutation
Phosphorylation
030215 immunology
Subjects
Details
- ISSN :
- 15409538 and 00221007
- Volume :
- 198
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....d24efe54d956b807491954e648c64ed4