Interleukin 5

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Interleukin 5
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Crystal structure of human IL-5
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols IL5 ; EDF; IL-5; TRF
External IDs OMIM147850 MGI96557 HomoloGene679 ChEMBL: 1169600 GeneCards: IL5 Gene
RNA expression pattern
File:PBB GE IL5 207952 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3567 16191
Ensembl ENSG00000113525 ENSMUSG00000036117
UniProt P05113 P04401
RefSeq (mRNA) NM_000879 NM_010558
RefSeq (protein) NP_000870 NP_034688
Location (UCSC) Chr 5:
132.54 – 132.56 Mb
Chr 11:
53.72 – 53.73 Mb
PubMed search [1] [2]

Interleukin 5 or IL-5 is an interleukin produced by T helper-2 cells and mast cells.

Function

Through binding to the IL-5 receptor, IL-5 stimulates B cell growth and increases immunoglobulin secretion. It is also a key mediator in eosinophil activation.

Structure

IL-5 is a 115-amino acid (in human, 133 in the mouse) -long TH2 cytokine that is part of the hematopoietic family. Unlike other members of this cytokine family (namely IL-3 and GM-CSF), this glycoprotein in its active form is a homodimer.[1]

Tissue expression

The IL-5 gene is located on chromosome 11 in the mouse, and chromosome 5 in humans, in close proximity to the genes encoding IL-3, IL-4, and granulocyte-macrophage colony-stimulating factor (GM-CSF),[2][3] which are often co-expressed in TH2 cells. Interleukin-5 is also expressed by eosinophils[4] and has been observed in the mast cells of asthmatic airways by immunohistochemistry.[5] IL-5 expression is regulated by several transcription factors including GATA3.[6]

Clinical significance

Interleukin-5 has long been associated with the cause of several allergic diseases including allergic rhinitis and asthma, wherein a large increase in the number of circulating, airway tissue, and induced sputum eosinophils have been observed.[7] Given the high concordance of eosinophils and, in particular, allergic asthma pathology, it has been widely speculated that eosinophils have an important role in the pathology of this disease.[8]

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.[9] 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,[10] is a major regulator of eosinophil accumulation in tissues, and can modulate eosinophil behavior at every stage from maturation to survival. Mepolizumab is a monoclonal antibody against IL-5 which can reduce excessive eosinophilia.

In Hodgkin lymphoma, for instance, the typically-observed eosinophilia is thought to be attributable to an increased production of IL-5.[11]

Interactions

Interleukin 5 has been shown to interact with Interleukin 5 receptor alpha subunit.[12][13][14]

Receptors

The IL-5 receptor is composed of an α and a βc chain.[15] The α subunit is specific for the IL-5 molecule, whereas the βc subunit also recognised by interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF).[15][16] Glycosylation of the Asn196 residue of the Rα subunit appears to be essential for binding of IL-5.[17]

References

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