The interleukin-5 receptor is a type I cytokine receptor. It is a heterodimer of the interleukin 5 receptor alpha subunit and CSF2RB.
The IL-5 receptor (IL-5R) belongs to the type I cytokine receptor family and is a heterodimer composed of two polypeptide chains, one ñ subunit, which binds IL-5 and confers upon the receptor cytokine specificity, and one ò subunit, which contains the signal transduction domains.
The IL-5Rñ chain is exclusively expressed by eosinophils, some basophils and murine B1 cells or B cell precursors. Like many other cytokine receptors, alternative splicing of the ñ-chain gene results in expression of either a membrane bound or soluble form of the bñ-chain. The soluble form does not lead to signal transduction and therefore has an antagonistic effect on IL-5 signaling. Both monomeric forms of IL-5Rñ are low affinity receptors, while dimerization with the ò-chain produces a high affinity receptor. In either case, the ñ-chain exclusively binds IL-5 and the intra-cellular portion of IL-5Rñ is associated with Janus kinase (JAK) 2, a protein tyrosine-kinase essential in IL-5 signal transduction.
The ò-subunit of the IL-5 receptor is responsible for signal transduction and contains several intracellular signaling domains. Unlike the ñ-chain, the ò-chain does not bind IL-5, is not specific to this cytokine, and is expressed on practically all leukocytes. In fact, the ò-subunit of the IL-5 receptor is also found in IL-3 and GM-CSF receptors where it is associated with IL-3Rñ and GM-CSFRñ subunits respectively. Therefore, it is known as the common ò receptor or òc. As with the IL-5Rñ subunit, the ò subunitâÂÂs cytoplasmic domain is constitutively associated with JAK2, as well as LYN, another tyrosine kinase, which are both essential for IL-5 signal transduction.
Three monoclonal antibodies are available to target IL-5R. Benralizumab binds to IL-5Ra, while mepolizumab and reslizumab bind to IL-5, preventing it from binding to IL-5Ra.