Interleukin 5 (IL5) is an
interleukin
Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and rela ...
produced by type-2
T helper cell
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are consider ...
s and
mast cells
A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granule (cell biology), granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the CFU-GEMM, ...
.
Function
Through binding to the
interleukin-5 receptor, interleukin 5 stimulates
B cell growth and increases
immunoglobulin
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
secretion - primarily
IgA Iga may refer to:
Arts and entertainment
* Ambush at Iga Pass, a 1958 Japanese film
* Iga no Kagemaru, Japanese manga series
* Iga, a set of characters from the Japanese novel '' The Kouga Ninja Scrolls''
Biology
* ''Iga'' (beetle), a gen ...
. It is also a key mediator in
eosinophil
Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. ...
activation.
Structure
IL-5 is a 115-
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
(in human, 133 in the mouse) -long TH2
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in a ...
that is part of the hematopoietic family. Unlike other members of this
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in a ...
family (namely
interleukin 3
Interleukin 3 (IL-3) is a protein that in humans is encoded by the ''IL3'' gene localized on chromosome 5q31.1. Sometimes also called colony-stimulating factor, multi-CSF, mast cell growth factor, MULTI-CSF, MCGF; MGC79398, MGC79399: the protein ...
and
GM-CSF), this glycoprotein in its active form is a homodimer.
Tissue expression
The IL-5
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
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
Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony-stimulating factor 2 (CSF2), is a monomeric glycoprotein secreted by macrophages, T cells, mast cells, natural killer cells, endothelial cells and fibroblasts th ...
(
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
A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granule (cell biology), granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the CFU-GEMM, ...
of asthmatic airways by
immunohistochemistry
Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to a ...
.
IL-5 expression is regulated by several
transcription factors
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...
including
GATA3.
Clinical significance
Interleukin-5 has long been associated with the cause of several allergic diseases including
allergic rhinitis
Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. Signs and symptoms include a runny or stuffy nose, sneezing, red, ...
and
asthma
Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, c ...
, wherein a large increase in the number of circulating, airway tissue, and induced
sputum
Sputum is mucus that is coughed up from the lower airways (the trachea and bronchi). In medicine, sputum samples are usually used for a naked eye examination, microbiological investigation of respiratory infections and cytological investigation ...
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.
Drugs that target IL-5 are
mepolizumab and
reslizumab.
Effect on eosinophils
Eosinophils are terminally differentiated
granulocytes
Granulocytes are
cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They ...
found in most
mammals
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fu ...
. The principal role of these cells, in a healthy host, is the elimination of antibody bound parasites through the release of
cytotoxic
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa'').
Cell physiology
Treating ...
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.
Mepolizumab is a monoclonal antibody antagonist IL-5 which can reduce excessive eosinophilia.
In
Hodgkin lymphoma
Hodgkin lymphoma (HL) is a type of lymphoma, in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the patient's lymph nodes. The condition ...
, for instance, the typically-observed
eosinophilia
Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds . Hypereosinophilia is an elevation in an individual's circulating blood eosinophil count above 1.5 x 109/ L (i.e. 1,500/ μL). The hypereosinophilic synd ...
is thought to be attributable to an increased production of IL-5.
Interactions
Interleukin 5 has been shown to
interact with
Interleukin 5 receptor alpha subunit.
Receptors
The IL-5 receptor is composed of an α and a βc chain.
The α subunit is specific for the IL-5 molecule, whereas the βc subunit also recognised by
interleukin 3
Interleukin 3 (IL-3) is a protein that in humans is encoded by the ''IL3'' gene localized on chromosome 5q31.1. Sometimes also called colony-stimulating factor, multi-CSF, mast cell growth factor, MULTI-CSF, MCGF; MGC79398, MGC79399: the protein ...
(IL3) and granulocyte-macrophage colony-stimulating factor (GM-CSF).
Glycosylation of the Asn196 residue of the Rα subunit appears to be essential for binding of IL-5.
References
External links
*
{{Authority control
Interleukins