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As their name implies, the IL-17 Receptors bind the IL-17 family of cytokines (IL-17A, A/F, B, C, D, E, and F). This family of receptors consists of 5 members (IL-17RA, RB, RC, RD, and RE). There is no particular structural similarity between the IL-17 receptors and any other family of receptors. The function of these receptors varies with their ligands. IL-17A and F are known for their inflammatory properties, while IL-17E (IL-25) promotes a Th2 response.
IL-17A IL-17B IL-17C Set 1 IL-17C Set 2
IL-17D IL-17E IL-17A/IL-17F/IL-17A/F IL-17RD
 
 
Description
IL-17A is the founding member of the IL-17 family, a group of six structurally related pro-inflammatory cytokines. IL-17A, secreted by activated CD4+ Th17 cell subpopulation, elicits multiple biological activities on a variety of cells including: the induction of IL-6, IL-8, G-CSF, and PGE2 production in epithelial, endothelial or fibroblasts; the enhancement of surface expression of ICAM-1 in fibroblasts; activation of NF-κB and costimulation of T cell proliferation. Recent studies demonstrated that, in mice, activated IL-17-secreting CD4+ helper T cells (Th17 cells)mediate an autoimmune arthritis that clinically and immunologically resembles rheumatoid arthritis (RA). Human IL-17A shows 63%, 63% and 72% amino acid sequence identity to rat IL-17A, mouse IL-17A and a protein encoded by the ORF13 gene of herpesvirus Saimiri (HVS), respectively. Both recombinant and natural IL-17A have been shown to exist as a disulfide-linked homodimeric glycoprotein containing two ~16 kD monomers.
Distribution
Cellular Sources: activated memory T lymphocytes, CD4+ T helper cells (Th17), neutrophils, CD8(+), NK, and gamma-delta T cells; Cellular Targets: Fibroblasts, epithelial and endothelial cells, stromal cells.
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Description
Six interleukin-17 (IL-17)-family (IL-17A-IL-17F) and five IL-17 receptor (IL-17R)-family (IL-17RA-IL-17RE) members have been reported in mammalian cells. IL-17RA (known as IL-17R, IL-17AR, CD217) is a 128-158 kD type I transmembrane glycoprotein. IL-17R binds to IL-17A (also known as IL-17, and CTLA-8, is a hallmarker of Th17 cells) and IL-17F and mediates the proinflammatory signals through interaction with IL-17RC or IL-17RD. IL-17R has broad tissue distribution, including fibroblasts, epithelial cells, endothelial cells, stromal cells, B cells, T cells, NK cells, monocytes and granulocytes.
Distribution
Broad tissue distribution, including fibroblasts, epithelial cells, endothelial cells, stromal cells, B cells, T cells, NK cells, monocytes and granulocytes.
Description
Also known as SEF, IL-17 RD is known to exist in several isoforms. IL-17 RD has been shown to form homomultimeric complexes. It can also complex with IL-17RA. Aside from IL-17A, no other ligands for these receptors have been identified. IL-17RD has been shown to be a feedback inhibitor of fibroblast growth factor mediated Ras-MAPK signaling and ERK activation. It may also mediate apoptosis, proliferation, migration, and angiogenesis.
Distribution
Endothelial cells, Epithelial cells.
Description
IL-17B is a protein also known as Cytokine CX1, NIRF, and Zcyto7. Originally referred to as IL-20, IL-17B is capable of stimulating the release of TNFα and IL-1β from a monocytic cell line. It is also known to promote proinflammatory responses.
Distribution
Cellular Sources: Cells of the gastrointestinal tract, pancreas, neurons, chondrocytes; Cellular Targets: Endothelial cells, neutrophils, keratinocytes.
Description
Also known as IL-25R, IL-17RB is a receptor for IL-17B and IL-17E (IL-25). It forms a homodimer for the binding of IL-17B, while forming a heterodimer with IL-17RA to serve as the receptor for IL-17E. It may also play a role in controlling the growth and/or differentiation of hematopoietic cells. IL-17RB has been shown to activate NF-κB and lead to the production of IL-8 (due to IL-17E binding). IL-17RB expression is strongly correlated with a Th2 response.
Distribution
Activated T cells, endothelial cells, endocrine tissue, macrophages, NKT cells (mice), CD4+ iNKT cells (mice), dendritic cells (human), basophils (human).
Description
IL-17C is a protein and a T cell-derived cytokine that shares the sequence similarity with IL-17. This cytokine was reported to stimulate the release of TNFα and IL-1β from a monocytic cell line. The expression of this cytokine was found to be very limited (adult prostate and fetal kidney) and restricted to activated T cells.
Distribution
Cellular Sources: Activated T cells, epithelial cells, cells of the prostate, lung, skin and fetal kidney; Cellular Targets: Epithelial cells.
Description
IL-17RE exists in multiple isoforms that can exist as a single-pass type 1 membrane protein, in a secreted form, or in the cytoplasm. IL-17RE binds with high affinity to IL-17C, but not IL1-7A, IL-17B, IL-17E, or IL-17F. Recently, it has been found to combine with IL-17RA to bind IL-17C. Combined with IL-17RA, this receptor is known to induce the production of anti-bacterial peptides and proinflammatory molecules.
Distribution
T cell subsets, epithelial cells of the lungs, gastrointestinal tract, skin, and lungs.
Description
IL-17D is a protein known to induce IL-6, IL-8, and GM-CSF production from endothelial cells. It is found to be preferentially expressed in skeletal muscle, brain, adipose, heart, lung, and pancreas tissues. Its receptors are currently unknown.
Distribution
Cellular Sources: Cells of the muscles, brain, heart, lung, pancreas and adipose tissue; Cellular Targets: Endothelial cells, myeloid progenitor cells.
Description
IL-25 (IL-17E) is a member of the IL-17 family of proinflammatory cytokines which include at least six members including IL-17A (IL-17), IL-17B, IL-17C, IL-17D, IL-17E (also called IL-25), and IL-17F. IL-17E is found at low levels in various peripheral tissues. It is a proinflammatory cytokine that promotes airway eosinophilia in mice. IL-17E plays a role in Th2 type inflammatory diseases, such as asthma and atopic dermatitis.
Distribution
Cellular Sources: Activated Th2 cells, bone marrow-derived mast cells, and alveolar macrophages , microglia; Cellular Targets: CD4+ NKT cells, macrophages, endothelial cells, Th2, and Th9 cells.
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Description
IL-17A/F is a heterodimer of IL-17A and IL-17F, two of the most studied members of the IL-17 family, consisting of at least six proinflammatory cytokines. Among the IL-17 family members, IL-17A and IL-17F share the highest sequence homology of 50%, and they are located on the same chromosome region. Earlier studies have shown that both IL-17A and IL-17F are produced as homodimers by Th17 cells, an activated subset of CD4+ T cells. However, recent studies demonstrate that the IL-17A/F heterodimer is also produced in Th17 cells, as a 40 kD, secreted, disulfide-linked glycoprotein. Functionally, IL-17A/F heterodimers signal through the same receptor as IL-17A and IL-17F homodimers and induce similar biological responses. However, both mouse and human IL-17A demonstrate more than 100-fold higher biological activity than IL-17F, while IL- 17A/F has intermediate activity. Both IL-17A and IL-17F have been associated with many inflammatory diseases in humans such as rheumatoid arthritis, multiple sclerosis, psoriasis, inflammatory bowel disease, and asthma. The exact cellular functions of IL-17A/F and its role in the disease processes are still not very clear. A convenient and ready-to-use IL-17A/F kit will be a very useful tool for those involved in the IL-17A, IL-17F, and IL-17A/F research efforts.
Distribution
Cellular Sources: activated memory T lymphocytes, CD4+ T helper cells (Th17), neutrophils, CD8(+), NK, and gamma-delta T cells; Cellular Targets: Fibroblasts, epithelial and endothelial cells, stromal cells.
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Description
IL-17F belongs to the IL-17 cytokine family which includes IL-17A, B, C, D, and E (also called IL-25). IL-17F shares the strongest homology to IL-17A. They share 50% amino acid sequence homology. The genes encoding IL-17 and IL-17F are localized in the same chromosomal region and are co-expressed by CD4+ and gamma delta T cells. Recently, an IL-17-IL-17F heterodimer was found to be expressed in Th17 cells together with IL-17 and IL-17F homodimers. Similar to IL-17, IL-17F utilizes IL-17RA and IL-17RC as its receptor and employs Act1 and TRAF6 as its signal transducers to induce the expression of pro-inflammatory cytokines and chemokines in many different cell types. IL-17F expression is upregulated in inflammatory bowel disease. A His161 to Arg161 (H161R) substitution in the third exon of the IL17F gene seems to be associated with asthma and chronic obstructive pulmonary disease (COPD) in Japanese subjects. In addition polymorphism of IL-17F seems to be associated to susceptibility to gastric cancer.
Distribution
Cellular Sources: T cells, Th17 cells, memory CD4 T cells, gamma delta T cells, activated monocytes; Cellular Targets: keratinocytes, fibroblasts, macrophages, neutrophils, epithelial cells, activated human mast cells, and basophils.
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Description
IL-17RC is a single pass transmembrane, 86kD protein that shares limited similarity with the interleukin 17 receptor. It is widely expressed in non leukocyte tissues and forms a heteromeric receptor for IL17 with IL-17RA. At least four different isoforms (ranging from 59 to 86kD) are known to exist. IL-17RC is expressed in heart, brain, intestine, liver, kidney, lung, muscle, placenta and prostate. Although IL-17RC is capable of binding to IL-17A, IL-17F, and IL-17A/F, IL-17RA is required for proper signaling.
Distribution
Broad tissue distribution, including epithelial cells, fibroblasts, Stromal cells, B cells, T cells, monocytes, NK cells.
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