Interleukin 29
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Interleukin-29 (IL-29) is a
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 autocrin ...
and it belongs to type III interferons group, also termed interferons λ (IFN-λ). IL-29 (alternative name IFNλ1) plays an important role in the
immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...
against pathogenes and especially against
viruses A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's ...
by mechanisms similar to type I interferons, but targeting primarily cells of
epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...
origin and
hepatocytes A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, ...
. IL-29 is encoded by the ''IFNL1''
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 ...
located on
chromosome 19 Chromosome 19 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 19 spans more than 58.6 million base pairs, the building material of DNA. It is considered the most gene-rich chromosom ...
in humans. It is a pseudogene in mice meaning the IL-29 protein is not produced in them.


Structure

IL-29 is, with the rest of IFN-λ, structurally related to the
IL-10 family The IL10 family is a family of interleukins. In addition to IL-10, it includes IL-19, IL-20, IL-22, IL-24 and IL-26. Some sources also include the interferons IL-28 and IL-29. The IL-10 family are helical cytokines categorized based on ...
, but its primary
amino acid sequence Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthe ...
(and also function) is more similar to type I interferons. It binds to a
heterodimeric In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...
receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
composed of one subunit IFNL1R specific for IFN-λ and a second subunit IL10RB shared among the IL-10 family cytokines.


Function


Effects on immune response to pathogenes  

IL-29 exhibits antiviral effects by inducing similar
signaling pathways Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...
as type I interferons. IL-29 receptor signals through JAK-STAT pathways leading to activated
expression Expression may refer to: Linguistics * Expression (linguistics), a word, phrase, or sentence * Fixed expression, a form of words with a specific meaning * Idiom, a type of fixed expression * Metaphorical expression, a particular word, phrase, o ...
of interferon-stimulated genes and production of antiviral proteins. Further consequences of IL-29 signalization comprise the
upregulated In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary pro ...
expression of MHC class I molecules, or enhanced expression of the costimulatory molecules and
chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In additio ...
receptors on pDC, which are the main producers of
IFN-α The type-I interferons (IFN) are cytokines which play essential roles in inflammation, immunoregulation, tumor cells recognition, and T-cell responses. In the human genome, a cluster of thirteen functional IFN genes is located at the 9p21.3 cyt ...
. IL-29 expression is dominant in virus-infected epithelial cells of the
respiratory The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies gre ...
,
gastrointestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
and
urogenital The genitourinary system, or urogenital system, are the organs of the reproductive system and the urinary system. These are grouped together because of their proximity to each other, their common embryological origin and the use of common pathwa ...
tracts, also in other mucosal tissues and
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different de ...
. Hepatocytes infected by HCV or HBV viruses stimulate the immune response by producing IL-29 (IFN-λ in general) rather than type I interferons. It is also produced by maturing macrophages, dendritic cells or mastocytes. It plays a role in defense against
pathogens In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a ger ...
apart from viruses. It affects the function of both
innate {{Short pages monitor