Interleukin 5 (IL-5) 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 related ...
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 considere ...
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 granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a ...
.
Function
Through binding to the
interleukin-5 receptor, interleukin 5 stimulates
B cell
B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasm ...
growth and increases
immunoglobulin secretion—primarily
IgA. It is also a key mediator in
eosinophil activation.
Structure
IL-5 is a 115-
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
(in human, 133 in the mouse) -long T
h2
cytokine
Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling.
Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
that is part of the hematopoietic family. Unlike other members of this cytokine family (namely
interleukin 3 and
GM-CSF), this glycoprotein in its active form is a homodimer.
Tissue expression
The IL-5
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
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),
which are often co-expressed in T
h2 cells. IL-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 granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a ...
of asthmatic airways by
immunohistochemistry
Immunohistochemistry is a form of immunostaining. It involves the process of selectively identifying antigens in cells and tissue, by exploiting the principle of Antibody, antibodies binding specifically to antigens in biological tissues. Alber ...
.
IL-5 expression is regulated by several
transcription factors including
GATA3.
Clinical significance
IL-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. It is classified as a type I hypersensitivity reaction. Signs a ...
and
asthma
Asthma is a common 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 wh ...
, 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 Cytopathology, cytological ...
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.
As of 2019, there are two FDA-approved
monoclonal antibodies
A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a Lineage (evolution), cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell.
Mon ...
that inhibit IL-5,
mepolizumab and
reslizumab. Additionally, the antibody
benralizumab blocks the
interleukin-5 receptor. All three drugs are used to treat severe
eosinophilic asthma and
eosinophilic granulomatosis with polyangiitis (EGPA). Another antibody,
depemokimab (
GSK3511294), ultra-long acting IL-5 inhibitor, is under development.
Some
hydroxyethylaminomethylbenzimidazole analogs have shown IL-5 inhibition ''
in vitro
''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
''.
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, that ...
found in most
mammals
A mammal () is a vertebrate animal of the class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three middle e ...
. 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.
Mepolizumab is a monoclonal antibody antagonist IL-5 which can reduce excessive eosinophilia.
In
Hodgkin lymphoma, the typically-observed
eosinophilia is thought to be attributable to an increased production of IL-5.
Interactions
IL-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 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF).
Glycosylation
Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not ...
of the
Asn196 residue of the Rα subunit appears to be essential for binding of IL-5.
References
External links
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Interleukins