Allergy‐associated Iϵ and Fcϵ receptor II (CD23b) genes activated via binding of an interleukin‐4‐induced transcription factor to a novel responsive element

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Abstract
Interleukin‐4 (IL‐4) has important regulatory functions in the immune system, particularly in the generation of immunoglobulin E, the principal mediator of allergic responses. The molecular basis of IL‐4 action has remained elusive so far. Here we report on a novel human transcription factor, termed nuclear factor IL‐4 (NF‐IL4), which is posttranslationally activated by IL‐4 in lymphoid and monocytic cells. Homologous binding sequences for NF‐IL4 were identified in the promoter regions of the IL‐4 controlled CD23b and Iϵ genes. We defined a palindromic 9‐bp consensus sequence (5′‐TYCYRRGAA‐3′) as IL‐4‐responsive element (IL‐4RE). Point mutation analysis of the CD23b promoter showed that binding of NF‐IL4 to the IL‐4RE is essential for the initiation of gene transcription in response to IL‐4. NF‐IL4 was not activated by Ca2+ ionophore, phorbol ester and cAMP either alone or in combination suggesting a non classical pathway for IL‐4 signal transduction.

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