Interleukin 22
Encyclopedia
Interleukin-22 is protein
that in humans is encoded by the IL22 gene
.
IL-22 a member of a group of cytokine
s called the IL-10
family or IL-10 superfamily (including IL-19
, IL-20
, IL-24
, and IL-26
), a class of potent mediators of cellular inflammatory responses. It shares use of IL-10R2 in cell signaling with other members of this family, IL-10, IL-26, IL-28A/B and IL-29. IL-22 is produced by activated DC
and T cell
s and initiates innate immune responses
against bacterial pathogens especially in epithelial cells such as respiratory and gut epithelial cells. IL-22 along with IL-17 is rapidly produced by splenic LTi-like cells and can be also produced by Th17 cells and likely plays a role in the coordinated response of both adaptive
and innate immune systems.
IL-22 biological activity is initiated by binding to a cell-surface complex composed of IL-22R1
and IL-10R2
receptor chains and further regulated by interactions with a soluble binding protein, IL-22BP, which shares sequence similarity with an extracellular region of IL-22R1 (sIL-22R1). IL-22 and IL-10 receptor chains play a role in cellular targeting and signal transduction
to selectively initiate and regulate immune responses. IL-22 can contribute to immune disease through the stimulation of inflammatory responses, S100s
and defensin
s. IL-22 also promotes hepatocyte
survival in the liver and epithelial cells in the lung and gut similar to IL-10. In some contexts, the pro-inflammatory versus tissue-protective functions of IL-22 are regulated by the often co-expressed cytokine IL-17A
receptor-related proteins CRF2-4 and IL-22R. It forms cell surface complexes with IL-22R1
and IL-10R2
chains resulting in signal transduction through receptor, IL-10R2. The IL-22/IL-22R1/IL-10R2 complex activates intracellular kinases (JAK1, Tyk2
, and MAP kinases) and transcription factors, especially STAT3
. It can induce IL-20
and IL-24
signaling when IL-22R1 pairs with IL-20R2.
cytokine. IL-22 binds to a heterodimeric cell surface receptor composed of IL-10R2
and IL-22R1
subunits.
Crystalization is possible if the N-linked glycosylation sites are removed in mutants of IL-22 bound with high-affinity cell-surface receptor sIL-22R1. The crystallographic asymmetric unit contained two IL-22-sIL-22R1 complexes.
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 IL22 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-22 a member of a group of 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...
s called the IL-10
Interleukin 10
Interleukin-10 , also known as human cytokine synthesis inhibitory factor , is an anti-inflammatory cytokine. In humans IL-10 is encoded by the IL10 gene....
family or IL-10 superfamily (including IL-19
Interleukin 19
Interleukin-19 is a cytokine that belongs to the IL-10 family of cytokines along with several other interleukins including IL-10, IL-20, IL-22, IL-24, IL-26, and several virus-encoded cytokines. It signals through the same cell surface receptor that is used by IL-20 and IL-24. The IL-19 gene is...
, IL-20
Interleukin 20
Interleukin-20 is a protein belonging to the IL-10 family of cytokines. IL-20 is produced by activated keratinocytes and monocytes and transmits an intracellular signal through two distinct cell-surface receptor complexes on keratinocytes and other epithelial cells...
, IL-24
Interleukin 24
Interleukin 24 is a cytokine belonging to the IL-10 family of cytokines that signals through two heterodimeric receptors: IL-20R1/IL-20R2 and IL-22R1/IL-20R2. This interleukin is also known as Melanoma differentiation-associated 7 due to its discovery as a tumour suppressing protein...
, and IL-26
Interleukin 26
Interleukin-26 is a protein that in humans is encoded by the IL26 gene.IL-26 is a 171-amino acid protein, which is similar in amino acid sequence to interleukin 10. It was originally called AK155 and is composed of a signal sequence, 6 helices, and 4 conserved cysteine residues...
), a class of potent mediators of cellular inflammatory responses. It shares use of IL-10R2 in cell signaling with other members of this family, IL-10, IL-26, IL-28A/B and IL-29. IL-22 is produced by activated DC
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...
and T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s and initiates innate immune responses
Innate immune system
The innate immune system, also known as non-specific immune system and secondary line of defence, comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner...
against bacterial pathogens especially in epithelial cells such as respiratory and gut epithelial cells. IL-22 along with IL-17 is rapidly produced by splenic LTi-like cells and can be also produced by Th17 cells and likely plays a role in the coordinated response of both adaptive
Adaptive immune system
The adaptive immune system is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogenic growth. Thought to have arisen in the first jawed vertebrates, the adaptive or "specific" immune system is activated by the “non-specific” and evolutionarily older innate...
and innate immune systems.
IL-22 biological activity is initiated by binding to a cell-surface complex composed of IL-22R1
Interleukin-22 receptor
Interleukin-22 receptor is a type II cytokine receptor. It binds to Interleukin-22. It is a heterodimer of α1 and α2 subunits....
and IL-10R2
Interleukin-10 receptor
Interleukin-10 receptor is a type II cytokine receptor. It consists of α and β subunits....
receptor chains and further regulated by interactions with a soluble binding protein, IL-22BP, which shares sequence similarity with an extracellular region of IL-22R1 (sIL-22R1). IL-22 and IL-10 receptor chains play a role in cellular targeting and signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
to selectively initiate and regulate immune responses. IL-22 can contribute to immune disease through the stimulation of inflammatory responses, S100s
S-100 protein
S-100 protein is a family of low molecular weight protein found in vertebrates characterized by two calcium binding sites of the helix-loop-helix conformation. There are at least 21 different types of S100 proteins...
and defensin
Defensin
Defensins are small cysteine-rich cationic proteins found in both vertebrates and invertebrates. They have also been reported in plants. They are, and function as, host defense peptides. They are active against bacteria, fungi and many enveloped and nonenveloped viruses. They consist of 18-45 amino...
s. IL-22 also promotes hepatocyte
Hepatocyte
A hepatocyte is a cell of the main tissue of the liver. Hepatocytes make up 70-80% of the liver's cytoplasmic mass.These cells are involved in:* Protein synthesis* Protein storage* Transformation of carbohydrates...
survival in the liver and epithelial cells in the lung and gut similar to IL-10. In some contexts, the pro-inflammatory versus tissue-protective functions of IL-22 are regulated by the often co-expressed cytokine IL-17A
Signaling
IL-22, signals through the interferonInterferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
receptor-related proteins CRF2-4 and IL-22R. It forms cell surface complexes with IL-22R1
Interleukin-22 receptor
Interleukin-22 receptor is a type II cytokine receptor. It binds to Interleukin-22. It is a heterodimer of α1 and α2 subunits....
and IL-10R2
Interleukin-10 receptor
Interleukin-10 receptor is a type II cytokine receptor. It consists of α and β subunits....
chains resulting in signal transduction through receptor, IL-10R2. The IL-22/IL-22R1/IL-10R2 complex activates intracellular kinases (JAK1, Tyk2
Tyrosine kinase 2
Non-receptor tyrosine-protein kinase TYK2 is an enzyme that in humans is encoded by the TYK2 gene.Tyk2 was the first member of the JAK family that was described...
, and MAP kinases) and transcription factors, especially STAT3
STAT3
Signal transducer and activator of transcription 3 also known as STAT3 is a transcription factor which in humans is encoded by the STAT3 gene.- Function :The protein encoded by this gene is a member of the STAT protein family...
. It can induce IL-20
Interleukin 20
Interleukin-20 is a protein belonging to the IL-10 family of cytokines. IL-20 is produced by activated keratinocytes and monocytes and transmits an intracellular signal through two distinct cell-surface receptor complexes on keratinocytes and other epithelial cells...
and IL-24
Interleukin 24
Interleukin 24 is a cytokine belonging to the IL-10 family of cytokines that signals through two heterodimeric receptors: IL-20R1/IL-20R2 and IL-22R1/IL-20R2. This interleukin is also known as Melanoma differentiation-associated 7 due to its discovery as a tumour suppressing protein...
signaling when IL-22R1 pairs with IL-20R2.
Structure
IL-22 is an α-helicalAlpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
cytokine. IL-22 binds to a heterodimeric cell surface receptor composed of IL-10R2
Interleukin-10 receptor
Interleukin-10 receptor is a type II cytokine receptor. It consists of α and β subunits....
and IL-22R1
Interleukin-22 receptor
Interleukin-22 receptor is a type II cytokine receptor. It binds to Interleukin-22. It is a heterodimer of α1 and α2 subunits....
subunits.
Crystalization is possible if the N-linked glycosylation sites are removed in mutants of IL-22 bound with high-affinity cell-surface receptor sIL-22R1. The crystallographic asymmetric unit contained two IL-22-sIL-22R1 complexes.