Interleukin 10
Encyclopedia
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"...

-10
(IL-10 or IL10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory
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...

 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...

. In humans IL-10 is encoded by the IL10 gene.

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...

 is produced primarily by monocyte
Monocyte
Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...

s and to a lesser extent by lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...

s. This cytokine has pleiotropic effects in immunoregulation and inflammation. It down-regulates the expression of Th1
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...

 cytokines, MHC class II antigens, and costimulatory molecules on macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...

s. It also enhances B cell survival, proliferation, and antibody production. This cytokine can block NF-κB activity, and is involved in the regulation of the JAK-STAT signaling pathway
JAK-STAT signaling pathway
The JAK-STAT signaling pathway transmits information from chemical signals outside the cell, through the cell membrane, and into gene promoters on the DNA in the cell nucleus, which causes DNA transcription and activity in the cell. The JAK-STAT system is a major signaling alternative to the second...

. Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract. and indeed patients with Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

 react favorably towards treatment with bacteria producing recombinant interleukin 10, showing the importance of interleukin 10 for counteracting excessive immunity in the human body.

A study in mice has shown that interleukin-10 is also produced by mast cell
Mast cell
A mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...

s, counteracting the inflammatory effect that these cells have at the site of an allergic reaction.

Function

It is capable of inhibiting synthesis of pro-inflammatory cytokines like IFN-γ
Interferon-gamma
Interferon-gamma is a dimerized soluble cytokine that is the only member of the type II class of interferons. This interferon was originally called macrophage-activating factor, a term now used to describe a larger family of proteins to which IFN-γ belongs...

, IL-2, IL-3
IL-3
IL-3 may refer to:* Interleukin 3* Illinois' 3rd congressional district* Illinois Route 3...

, TNFα and GM-CSF made by cells such as macrophages and regulatory T-cells

IL-10 also displays potent abilities to suppress the antigen presentation capacity of antigen presenting cells.

However, it is also stimulatory towards certain T cells, mast cells and stimulates B cell maturation and antibody production.

Expression

It is mainly expressed in monocyte
Monocyte
Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...

s and Type 2 T helper cells (TH2), mast cells, CD4+CD25+Foxp3+ regulatory T cells, and also in a certain subset of activated T cells and B cells. Said et al. showed that IL-10 can also be produced by monocytes upon PD-1 triggering in this cells.

It is released by cytotoxic T-cells to inhibit the actions of NK cells during the immune response to viral
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...

 infection.

Gene and protein structure

In humans, the IL-10 gene is located in 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...

 1 and consists of 5 exons.

The IL-10 protein is a homodimer
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...

 . Each subunit is 178 amino acids long.

Interleukin 10 is classified as a class 2 cytokine. The Class 2 alpha-helical cytokines consist of interleukin-10 (IL-10), IL-19,
IL-20, IL-22, IL-24 (Mda-7), and IL-26, interferons (IFN-alpha, -beta, -epsilon, -kappa, -omega, -delta, -tau, and -gamma) and interferon-like molecules (limitin, IL-28A, IL-28B, and IL-29)

Interactions

Interleukin 10 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 10 receptor, alpha subunit
Interleukin 10 receptor, alpha subunit
Interleukin 10 receptor, alpha subunit is a subunit for the interleukin-10 receptor. IL10RA, is its human gene.IL10RA has also recently been designated CDW210A .-Interactions:...

.

The receptor complex for interleukin-10 also requires the IL10R2 chain to initiate signaling. This ligand:receptor combination is found in birds and frogs, and likely also exists in bony fish.

External links

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