Interleukin-4 signaling pathway (IL-4 signaling pathway)

The interleukin‐4 signaling pathway is a critical immune regulatory network initiated when interleukin‐4 binds its cell surface receptors—type I or type II interleukin‐4 receptors—which are composed primarily of the shared subunit interleukin‐four receptor alpha (IL‐⁠⁠⁠⁠⁠⁴⁄₄). This interaction triggers dimerization with either common gamma chain (γc) in hematopoietic cells or with interleukin‐13 receptor alpha (IL‐13Rα₁) in nonhematopoietic tissues. Upon ligand binding, these complexes activate intracellular kinases such as JAKs leading to phosphorylation events that recruit adaptor proteins like IRS and transcription factors such as STAT6. Activated STAT6 translocates into the nucleus where it drives gene expression programs responsible for T helper type 2 (TH₂) cell differentiation, immunoglobulin E (IgE) class switching in B cells, mucus production by epithelial cells, chemotaxis/migration of mast cells/basophils/eosinophils, neuronal survival/differentiation effects—and overall orchestration of allergic inflammation and certain neuroprotective functions. Dysregulation contributes significantly to asthma/allergy pathogenesis but also plays roles in autoimmunity and neurological disorders[1][2][3][5].

Other names

IL-4/IL-13 signalingInterleukin 4/13 receptor pathways

Antagonism/blockade of interleukin‑4 binding to its receptor subunit(s), especially IL‑4Rα, thereby inhibiting downstream JAK/STAT6 activation and TH2 immune responses. Inhibition of IgE synthesis by B cells. Suppression of allergic inflammation.