Interleukin-22 (IL-22) is
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''IL22''
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 ...
.
Structure
IL-22 is an
α-helical cytokine. IL-22 binds to a heterodimeric cell surface receptor composed of
IL-10R2 and
IL-22R1 subunits.
IL-22R is expressed on tissue cells, and it is absent on immune cells.
Crystallization 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.
Function
IL-22 is produced by several populations of immune cells at a site of
inflammation
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
. Producers are αβ
T cells
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell re ...
classes Th1 cell, Th1, Th22 and T helper 17 cell, Th17 along with γδ
T cells
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell re ...
, NKT cell, NKT, Type 3 innate lymphoid cells, ILC3, Neutrophil, neutrophils and Macrophage, macrophages. IL-22 takes effect on non-hematopoietic cells – mainly Stromal cell, stromal and Epithelium, epithelial cells. Effects involve stimulation of cell survival, proliferation and synthesis of antimicrobials including S100 protein, S100, Reg3β, REG3G, Reg3γ and Defensin, defensins. IL-22 thus participates in both wound healing and in protection against Microorganism, microbes.
IL-22 dysregulation takes part in pathogenesis of several Autoimmune disease, autoimmune diseases like systemic lupus erythematosus, rheumatoid arthritis and psoriasis.
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, S-100 protein, S100s and defensins. 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
Target tissue
Targets of this cytokine are mostly non-hematopoietic cells – Epithelium, epithelial and Stromal cell, stromal cells of following tissues and organs: liver, lung, skin, thymus, pancreas, kidney, gastrointestinal tract, Synovial Tissue, synovial tissues, heart, breast, eye and adipose tissue.
Signaling
IL-22 is a member of a group of cytokines called the Interleukin 10, IL-10 family or IL-10 superfamily (including Interleukin 19, IL-19, Interleukin 20, IL-20, Interleukin 24, IL-24, and Interleukin 26, 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, signals through the interferon 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, Tyrosine kinase 2, Tyk2, and MAP kinases) and transcription factors, especially STAT3. It can induce Interleukin 20, IL-20 and Interleukin 24, IL-24 signaling when IL-22R1 pairs with IL-20R2.
Regulation of production
IL-22 production is induced mainly through Interleukin-23 receptor, IL-23 receptor signalling. IL-23 is produced by Dendritic cell, dendritic cells after recognition of Ligand, ligands by specific Toll-like receptor, Toll-like receptors especially in combination with CLEC7A, Dectin-1 and or NOD2 signalling. Interleukin 1 beta, IL-1β stimulates IL-22 production too. On the other hand IL-22 binding protein is a soluble inhibitor which blocks receptor binding site of IL-22.
References
Further reading
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{{Interleukin receptor modulators
Interleukins