Interleukin 13
Encyclopedia
Interleukin 13 is a protein
that in humans is encoded by the IL13 gene
. IL-13 is cytokine
secreted by many cell types, but especially T helper
type 2 (Th2) cells, that is a mediator of allergic inflammation
and disease.
, IL-13 is more importantly implicated as a central mediator of the physiologic changes induced by allergic inflammation in many tissues. IL-13 induces its effects through a multi-subunit receptor that includes the alpha chain of the IL-4 receptor
(IL-4Rα) and at least one of two known IL-13-specific binding chains. Most of the biological effects of IL-13, like those of IL-4, are linked to a single transcription factor
, signal transducer and activator of transcription 6 (STAT6). This can be resulted from an allergic reaction brought about when facing an Ala gene.
The functions of IL-13 overlap considerably with those of IL-4, especially with regard to changes induced on hematopoietic cells, but these effects are probably less important given the more potent role of IL-4. Thus, although IL-13 can induce immunoglobulin E
(IgE) secretion from activated human B cell
s, deletion of IL-13 from mice does not markedly affect either Th2 cell development or antigen-specific IgE responses induced by potent allergen
s. In comparison, deletion of IL-4 abrogates these responses. Thus, rather than a lymphoid cytokine, IL-13 acts more prominently as a molecular bridge linking allergic inflammatory cells to the non-immune cells in contact with them, thereby altering physiological function.
Although IL-13 is associated primarily with the induction of airway disease, it also has anti-inflammatory
properties. Airway matrix metalloproteinase
s (MMPs), which are protein-degrading enzymes, are required to induce egression of effete parenchyma
l inflammatory cells into the airway lumen where they are then cleared. Among other factors, IL-13 induces these MMPs as part of a mechanism that protects against excessive allergic inflammation that predisposes to asphyxiation.
organs that are required to expel the offending organisms or their products. For example, expulsion from the gut of a variety of mouse helminths requires IL-13 secreted by Th2 cells. IL-13 induces several changes in the gut that create an environment hostile to the parasite, including enhanced contractions and glycoprotein
hyper-secretion from gut epithelial
cells, that ultimately lead to detachment of the organism from the gut wall and their removal.
The eggs of the parasite Schistosoma mansoni
may lodge in a variety of organs including the gut wall, liver, lung and even central nervous system, inducing the formation of granuloma
s under the control of IL-13. Here, however, the eventual result is organ damage and often profound or even fatal disease, not resolution of the infection. An emerging concept is that IL-13 may antagonize Th1 responses that are required to resolve intracellular infection
s. In this immune dysregulated context, marked by the recruitment of aberrantly large numbers of Th2 cells, IL-13 inhibits the ability of host immune cells to destroy intracellular
pathogen
s.
IL-13 induces many features of allergic lung disease, including airway hyperresponsiveness, goblet cell
metaplasia
and mucus hypersecretion, which all contribute to airway obstruction. IL-4 contributes to these physiologic changes, but is less important than IL-13. IL-13 also induces secretion of chemokine
s that are required for recruitment of allergic effector cells to the lung. Studies of STAT6 transgenic mice suggest the interesting possibility that IL-13 signaling occurring only through the airway epithelium is required for most of these effects. While no studies have yet directly implicated IL-13 in the control of human diseases, many polymorphism
s in the IL-13 gene have been shown to confer an enhanced risk of atopic respiratory diseases such as asthma
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the IL13 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...
. IL-13 is 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...
secreted by many cell types, but especially 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...
type 2 (Th2) cells, that is a mediator of allergic inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
and disease.
Functions
In addition to effects on immune cells that are similar to those of the closely related cytokine IL-4Interleukin 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...
, IL-13 is more importantly implicated as a central mediator of the physiologic changes induced by allergic inflammation in many tissues. IL-13 induces its effects through a multi-subunit receptor that includes the alpha chain of the IL-4 receptor
Interleukin-4 receptor
Interleukin 4 receptor is a type I cytokine receptor. IL4R is its human gene.-Interactions:Interleukin-4 receptor has been shown to interact with SHC1.-Further reading:-External links:...
(IL-4Rα) and at least one of two known IL-13-specific binding chains. Most of the biological effects of IL-13, like those of IL-4, are linked to a single transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
, signal transducer and activator of transcription 6 (STAT6). This can be resulted from an allergic reaction brought about when facing an Ala gene.
The functions of IL-13 overlap considerably with those of IL-4, especially with regard to changes induced on hematopoietic cells, but these effects are probably less important given the more potent role of IL-4. Thus, although IL-13 can induce immunoglobulin E
Immunoglobulin E
Immunoglobulin E is a class of antibody that has been found only in mammals. IgE is a monomeric antibody with 4 Ig-like domains...
(IgE) secretion from activated human 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...
s, deletion of IL-13 from mice does not markedly affect either Th2 cell development or antigen-specific IgE responses induced by potent allergen
Allergen
An allergen is any substance that can cause an allergy. In technical terms, an allergen is a non-parasitic antigen capable of stimulating a type-I hypersensitivity reaction in atopic individuals....
s. In comparison, deletion of IL-4 abrogates these responses. Thus, rather than a lymphoid cytokine, IL-13 acts more prominently as a molecular bridge linking allergic inflammatory cells to the non-immune cells in contact with them, thereby altering physiological function.
Although IL-13 is associated primarily with the induction of airway disease, it also has anti-inflammatory
Anti-inflammatory
Anti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system....
properties. Airway matrix metalloproteinase
Matrix metalloproteinase
Matrix metalloproteinases are zinc-dependent endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzincin superfamily....
s (MMPs), which are protein-degrading enzymes, are required to induce egression of effete parenchyma
Parenchyma
Parenchyma is a term used to describe a bulk of a substance. It is used in different ways in animals and in plants.The term is New Latin, f. Greek παρέγχυμα - parenkhuma, "visceral flesh", f. παρεγχεῖν - parenkhein, "to pour in" f. para-, "beside" + en-, "in" + khein, "to pour"...
l inflammatory cells into the airway lumen where they are then cleared. Among other factors, IL-13 induces these MMPs as part of a mechanism that protects against excessive allergic inflammation that predisposes to asphyxiation.
Clinical significance
IL-13 specifically induces physiological changes in parasitizedParasitism
Parasitism is a type of symbiotic relationship between organisms of different species where one organism, the parasite, benefits at the expense of the other, the host. Traditionally parasite referred to organisms with lifestages that needed more than one host . These are now called macroparasites...
organs that are required to expel the offending organisms or their products. For example, expulsion from the gut of a variety of mouse helminths requires IL-13 secreted by Th2 cells. IL-13 induces several changes in the gut that create an environment hostile to the parasite, including enhanced contractions and glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
hyper-secretion from gut epithelial
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
cells, that ultimately lead to detachment of the organism from the gut wall and their removal.
The eggs of the parasite Schistosoma mansoni
Schistosoma mansoni
Schistosoma mansoni is a significant parasite of humans, a trematode that is one of the major agents of the disease schistosomiasis. The schistosomiasis caused by Schistosoma mansoni is intestinal schistosomiasis....
may lodge in a variety of organs including the gut wall, liver, lung and even central nervous system, inducing the formation of granuloma
Granuloma
Granuloma is a medical term for a tiny collection of immune cells known as macrophages. Granulomas form when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate. Such substances include infectious organisms such as bacteria and fungi as well as...
s under the control of IL-13. Here, however, the eventual result is organ damage and often profound or even fatal disease, not resolution of the infection. An emerging concept is that IL-13 may antagonize Th1 responses that are required to resolve intracellular infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s. In this immune dysregulated context, marked by the recruitment of aberrantly large numbers of Th2 cells, IL-13 inhibits the ability of host immune cells to destroy intracellular
Intracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
s.
IL-13 induces many features of allergic lung disease, including airway hyperresponsiveness, goblet cell
Goblet cell
Goblet cells are glandular simple columnar epithelial cells whose sole function is to secrete mucin, which dissolves in water to form mucus. They use both apocrine and merocrine methods for secretion....
metaplasia
Metaplasia
Metaplasia is the reversible replacement of one differentiated cell type with another mature differentiated cell type. The change from one type of cell to another may generally be a part of normal maturation process or caused by some sort of abnormal stimulus...
and mucus hypersecretion, which all contribute to airway obstruction. IL-4 contributes to these physiologic changes, but is less important than IL-13. IL-13 also induces secretion of chemokine
Chemokine
Chemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...
s that are required for recruitment of allergic effector cells to the lung. Studies of STAT6 transgenic mice suggest the interesting possibility that IL-13 signaling occurring only through the airway epithelium is required for most of these effects. While no studies have yet directly implicated IL-13 in the control of human diseases, many polymorphism
Polymorphism (biology)
Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
s in the IL-13 gene have been shown to confer an enhanced risk of atopic respiratory diseases such as 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...
.