The interleukin 4 receptor is a type I cytokine receptor. It is a heterodimer, that is, composed of two subunits. IL4R is the human gene coding for IL-4Rα, the subunit which combines with either common gamma chain (γc, forming the type I IL4 receptor) or with IL-13Rα1 (forming the type II IL4 receptor).[5]
Function
This gene encodes the alpha chain of the interleukin-4 receptor, a type I transmembrane protein that can bind interleukin 4 and interleukin 13 to regulate IgEantibody production in B cells. Among T cells, the encoded protein also can bind interleukin 4 to promote differentiation of Th2 cells. A soluble form of the encoded protein can be produced by an alternate splice variant or by proteolysis of the membrane-bound protein, and this soluble form can inhibit IL4-mediated cell proliferation and IL5 upregulation by T-cells. Allelic variations in this gene have been associated with atopy, a condition that can manifest itself as allergic rhinitis, sinusitis, asthma, or eczema. Two transcript variants encoding different isoforms, a membrane-bound and a soluble form, have been found for this gene.[6] Interactions of IL-4 with TNFα promote structural changes to vascular endothelial cells, thus playing an important role in tissue inflammation.[7]
The binding of IL-4 or IL-13 to the IL-4 receptor on the surface of macrophages results in the alternative activation of those macrophages. Alternatively activated macrophages (AAMΦ) downregulate inflammatory mediators such as IFNγ during immune responses, particularly with regards to helminth infections.[8]
The N-terminal (extracellular) portion of interleukin-4 receptor is related in overall topology to fibronectin type III modules and folds into a sandwich comprising seven antiparallelbeta sheets arranged in a three-strand and a four-strand beta-pleated sheet. They are required for binding of interleukin-4 to the receptor alpha chain, which is a crucial event for the generation of a Th2-dominated early immune response.[11]
^Ikizawa K, Yanagihara Y (February 2000). "Possible involvement of Shc in IL-4-induced germline epsilon transcription in a human B cell line". Biochemical and Biophysical Research Communications. 268 (1): 54–59. doi:10.1006/bbrc.2000.2080. PMID10652211.
Nelms K, Keegan AD, Zamorano J, Ryan JJ, Paul WE (1999). "The IL-4 receptor: signaling mechanisms and biologic functions". Annual Review of Immunology. 17 (1): 701–738. doi:10.1146/annurev.immunol.17.1.701. PMID10358772.
