Interleukin 5
Encyclopedia
Interleukin 5 or IL-5 is an interleukin
Interleukin
Interleukins are a group of cytokines that were first seen to be expressed by white blood cells . The term interleukin derives from "as a means of communication", and "deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes"...

 produced by T helper
T helper cell
T helper cells are a sub-group of lymphocytes, a type of white blood cell, that play an important role in the immune system, particularly in the adaptive immune system. These cells have no cytotoxic or phagocytic activity; they cannot kill infected host cells or pathogens. Rather, they help other...

-2 cells and mast cells. Its functions are to stimulate B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...

 growth and increase immunoglobulin secretion. It is also a key mediator in eosinophil activation. IL-5 is a 115-amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 (in human, 133 in the mouse) -long TH2 cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

 that is part of the hematopoietic family. Unlike other members of this cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

 family (namely IL-3
Interleukin 3
Interleukin 3, also known as IL-3, is a protein that in humans is encoded by the IL3 gene.-Function:Interleukin-3 is an interleukin, a type of biological signal that can improve the body's natural response to disease as part of the immune system...

 and GM-CSF) , this glycoprotein in its active form is a homodimer. The IL-5 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

 is located on chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

 11 (in the mouse, chromosome 5 in humans) in close proximity to the genes encoding IL-3
Interleukin 3
Interleukin 3, also known as IL-3, is a protein that in humans is encoded by the IL3 gene.-Function:Interleukin-3 is an interleukin, a type of biological signal that can improve the body's natural response to disease as part of the immune system...

, IL-4
Interleukin 4
Interleukin-4, abbreviated IL-4, is a cytokine that induces differentiation of naive helper T cells to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4. The cell that initially produces IL-4, thus inducing Th0 differentiation, has not been identified, but recent...

, 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
Immunohistochemistry
Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...

. IL-5 expression is regulated by several transcription factors including GATA3
GATA3
Trans-acting T-cell-specific transcription factor GATA-3 is a protein that in humans is encoded by the GATA3 gene.GATA-3 belongs to the GATA family of transcription factors. The protein contains two GATA-type zinc fingers and is an important regulator of T cell development and plays an important...

.

Clinical significance

Interleukin-5 has long been associated with the cause of several allergic diseases including allergic rhinitis
Allergic rhinitis
Allergic rhinitis, also known as pollenosis or hay fever, is an allergic inflammation of the nasal airways.It occurs when an allergen, such as pollen, dust or animal dander is inhaled by an individual with a sensitized immune system...

 and asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...

, wherein a large increase in the number of circulating, airway tissue, and induced sputum
Sputum
Sputum is mucus that is coughed up from the lower airways. It is usually used for microbiological investigations of respiratory infections....

 eosinophils have been observed. 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.

The IL-5 Receptor

The IL-5 receptor (IL-5R) belongs to the type I cytokine receptor
Type I cytokine receptor
Type I cytokine receptors are transmembrane receptors expressed on the surface of cells that recognize and respond to cytokines with four α-helical strands. These receptors are also known under the name hemopoietin receptors, and share a common amino acid motif in the extracellular portion...

 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
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...

 domains.

α-subunit

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
Alternative splicing
Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...

 of the α-chain gene results in expression of either a membrane bound or soluble form of the bα-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
Janus kinase
Janus kinase is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. They were initially named "just another kinase" 1 & 2 , but were ultimately published as "Janus kinase"...

 (JAK
Jak
Jak may refer to:*JAK, Jazakomu Allahu Khayran *JAK members bank, a Swedish interest-free bank*Janus kinase, an intracellular signaling molecule; component of the JAK-STAT signal system...

) 2, a protein tyrosine-kinase essential in IL-5 signal transduction.

β-subunit

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
Interleukin 3
Interleukin 3, also known as IL-3, is a protein that in humans is encoded by the IL3 gene.-Function:Interleukin-3 is an interleukin, a type of biological signal that can improve the body's natural response to disease as part of the immune system...

 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. As with the IL-5Rα subunit, the β subunit’s cytoplasmic domain is constitutively associated with JAK2, as well as LYN
LYN
Tyrosine-protein kinase Lyn is a protein that in humans is encoded in humans by the LYN gene.Lyn is a member of the Src family of protein tyrosine kinases, which is mainly expressed in hematopoietic cells, in neural tissues liver, and adipose tissue. In various hematopoietic cells, Lyn has emerged...

, 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.

Interactions

Interleukin 5 has been shown to interact
Protein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with Interleukin 5 receptor alpha subunit
Interleukin 5 receptor alpha subunit
Interleukin 5 receptor, alpha also known as CD125 is a subunit of the Interleukin-5 receptor. IL5RA also denotes its human gene.-Interactions:...

.
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