Cutting edge: Effects of an allergy-associated mutation in the human IL-4Ralpha (Q576R) on human IL-4-induced signal transduction

ii mutation in the human (hu) IL-4R alpha, Q576R, has been linked with alle rgy in humans. Increased sensitivity of patients cells with this mutation t o lL-4 suggest that a Q576R change enhances IL-4 signaling. To directly tes t this hypothesis, we analyzed the ability of huIL-4R alpha cDNA bearing th e Q576R and Y575F mutations to signal tyrosine phosphorylation, DNA-binding activity, proliferation, protection from apoptosis, and CD23 induction in response to huIL-4 in murine cells, Responses generated by the Q576R and Y5 75F mutants were similar to those of the wild-type receptor, using various concentrations of huIL- 4 and times of stimulation. These results indicate that neither the Q576R nor the Y575F mutations have a significant direct ef fect on IL-4 signal transduction, and that hypersensitive induction of CD23 in cells derived from human allergy patients may be due to different and/o r additional alterations in the IL-4 signaling pathway,