Interleukin 5 (colony-stimulating factor, eosinophil)
|Crystal structure of human IL-5|
|RNA expression pattern|
Interleukin 5 or IL-5 is an interleukin produced by T helper-2 cells and mast cells. Its functions are to stimulate B cell growth and increase immunoglobulin secretion. It is also a key mediator in eosinophil activation. IL-5 is a 115 amino acid (in man, 133 in the mouse) long TH2 cytokine which is part of the hematopoietic family. Unlike other members of this cytokine family (namely IL-3 and GM-CSF) , in its active form, this glycoprotein is a homodimer . The IL-5 gene is located on chromosome 11 (in the mouse, chromosome 5 in humans) in close proximity to the genes encoding IL-3, IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF)  which are often co-expressed in TH2 cells. Interleukin-5 is also expressed by eosinophils  and has been observed in the mast cells of asthmatic airways by immunohistochemistry . IL-5 expression is regulated by several transcription factors including GATA-3 .
Interleukin-5 has long been associated with several allergic diseases including allergic rhinitis and asthma where a large increase in the number of circulating, airway tissue, and induced sputum eosinophil numbers have been observed . Given the high concordance of eosinophils and, particularly, allergic asthma pathology, it has been widely speculated that eosinophils have an important role in the pathology of this disease .
The IL-5 Receptor
The IL-5 receptor (IL-5R) belongs to the type I cytokine receptor family and is a heterodimer composed of two polypeptide chains, one α subunit which binds IL-5 and confers upon the receptor cytokine specificity, and one β subunit which contains the signal transduction domains.
The IL-5Rα 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 α-chain gene results in expression of either a membrane bound or soluble form of the α-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-5Rα are low affinity receptors, while dimerization with the β-chain produces a high affinity receptor . In either case, the α-chain exclusively binds IL-5 and the intra-cellular portion of IL-5Rα is associated with Janus kinase (JAK) 2, a protein tyrosine-kinase essential in IL-5 signal transduction .
The β-subunit of the IL-5 receptor is responsible for signal transduction and contains several intracellular signaling domains. Unlike the α-chain, the β-chain does not bind IL-5, is not specific to this cytokine, and is expressed on practically all leukocytes. In fact, the β-subunit of the IL-5 receptor is also found in IL-3 and GM-CSF receptors where it is associated the IL-3Rα and GM-CSFRα subunits respectively . Therefore it is known as the common β receptor or βc. Like the IL-5Rα subunit, the β subunit’s cytoplasmic domain is constitutively associated with JAK2 , as well as LYN, another tyrosine kinase, which are both essential for IL-5 signal transduction .
Effect of IL-5 on Eosinophils
Eosinophils are terminally differentiated granulocytes found in most mammals. The principal role of these cells, in a healthy host, is the elimination of antibody bound parasites through the release of cytotoxic granule proteins . Given that eosinophils are the primary IL-5Rα expressing cells, it is not surprising that this cell type responds to IL-5. In fact, IL-5 was originally discovered as an eosinophil colony stimulating factor , is a major regulator of eosinophil accumulation in tissues, and can modulate eosinophil behavior at every stage from maturation to survival.
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|IL-1 superfamily||IL-1 (IL-1Ra) - IL-18 - IL-33|
|IL-6 like/gp130 utilizing||IL-6 - IL-11 - IL-27 - IL-30 - IL-31|
|IL-10 family||IL-10 - IL-19 - IL-20 - IL-22 - IL-24 - IL-26|
|Interferon type III||IL-28 - IL-29|
|Common γ-chain family||IL-2/IL-15 - IL-3 - IL-4 - IL-7 - IL-9 - IL-13 - IL-21|
|IL-12 family||IL-12 - IL-23 - IL-27 - IL-35|
|Other||IL-5 - IL-8 - IL-14 - IL-16 - IL-17/IL-25 (A) - IL-32|