Interleukin-21 receptor, also known as IL-21 receptor, IL-21R, Novel interleukin receptor, IL21R, and NILR, is a single-pass type I membrane protein that belongs to the type I cytokine receptor family and Type 4 subfamily. Interleukin-21 (IL-21) belongs to a family of cytokines that bind to a composite receptor consisting of a private receptor (IL-21R) and the common cytokine receptor gamma chain ( gamma(C) ). The IL-21R is discovered as a novel member of the class-I-cytokine-receptor family and is selectively expressed in lymphoid tissues. IL-21R shows strong sequence homologies to the interleukin-4 receptor alpha chain gene (IL-4RA). The WSXWS motif of IL-21R appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding. The box 1 motif of IL-21R is required for JAK interaction and/or activation. The IL-21R is widely distributed on lymphohematopoietic cells and IL21 impacts some cell types, including CD8+ memory T cells, NK cells, and subsets of CD4 memory T cells. Increased IL21 production is characteristic of certain autoimmune diseases and is likely to contribute to autoantibody production as well as pathological features of autoimmune disease. The critical role of IL21 in promoting humoral immune responses makes it an important focus of potential therapeutic interventions in conditions characterized by the overproduction of pathogenic autoantibodies.
Cytokine that contributes to the inflammatory response in vivo.
Interleukin-22 (IL-22) was initially identified as a gene induced by IL-9 in mouse T cells and mast cells. Mouse IL-22 cDNA encodes a 179 amino acid residue protein with a putative 33 amino acid signal peptide that is cleaved to generate a 147 amino acid mature protein that shares approximately 79% and 22% sequence identity with human IL22 and IL10, respectively. IL22 has been shown to activate STAT-1 and STAT-3 in several hepatoma cell lines and up-regulate the production of acute phase proteins. IL-22 is produced by normal mouse T cells upon Con A activation. Mouse IL-22 expression is also induced in various organs upon lipopolysaccharide injection, suggesting that IL-22 may be involved in inflammatory responses. The functional IL-22 receptor complex consists of two receptor subunits, IL-22R (previously an orphan receptor named CRF2-9) and IL-10Rβ (previously known as CRF2-4), belonging to the class II cytokine receptor family.
Interleukin 23 (IL-23) is a heterodimeric cytokine composed of two disulfide-linked subunits, a p19 subunit that is unique to IL-23, and a p40 subunit that is shared with IL-12. The p19 subunit has homology to the p35 subunit of IL-12, as well as to other single chain cytokines such as IL-6 and IL-11. The p40 subunit is homologous to the extracellular domains of the hematopoietic cytokine receptors. Although p19 is expressed by activated macrophages, dendritic cells, T cells, and endothelial cells, only activated macrophages and dendritic cells express p40 concurrently to produce IL-23. IL-23 has biological activities that are similar to, but distinct from IL-12. Both IL-12 and IL-23 induce proliferation and IFN-gamma production by human T cells. While IL-12 acts on both naive and memory human T cells, the effects of IL-23 is restricted to memory T cells.
IL-23, which is mainly secreted by antigen-presenting cells, is a member of the IL-12 family, which includes IL-12, IL-27, and IL-35. IL-23 is a heterodimeric cytokine, comprised of a unique p19 subunit and p4 subunit, the latter of which is shared with IL-12. The receptor for IL-23 consists of IL-23R and IL-12Rβ1, the latter of which is also characteristic of IL-12. IL-23 is essential for Th17 differentiation, expansion, and survival by binding to its receptor, thereby activating the signaling pathway. Many studies revealed that the IL-23/Th17 pathway is implicated in the pathophysiology of various autoimmune diseases, such as autoimmune arthritis, primary biliary cirrhosis, and inflammatory bowel disease.
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