Disease relevance of IL17RA

• Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth-related oncogene-alpha and granulocyte colony-stimulating factor in bronchial epithelium: implications for airway inflammation in cystic fibrosis [1].
• OBJECTIVE: To evaluate the presence of interleukin-17 (IL-17) and the expression of IL-17 receptor (IL-17R) in joint tissues from subjects with different arthritides [2].
• Chondrocytes from all types of arthritides were negative for IL-17 staining, but expressed IL-17R; the highest percentage of positive chondrocytes was found in seronegative spondylarthritis and the lowest in RA [2].
• NK cells and U-2 OS, MG-63, HOS osteosarcoma cell lines express the IL-17 receptor, the highest amount being found on U-2 OS [3].
• In validation studies, immunohistochemical staining and Western blot analysis were used to detect interleukin (IL)-17 and IL-17 receptor (IL-17R) in nasal polyps and controls [4].

High impact information on IL17RA

• Whereas expression of IL-17 is restricted to activated T cells, the IL-17 receptor is found to be widely expressed, a finding consistent with the pleiotropic activities of IL-17 [5].
• Strikingly, treatment with IL-17A or IL-17F markedly reduced FRET efficiency, suggesting that IL-17RA subunits within the IL-17R complex undergo a conformational change upon ligand binding [6].
• We used fluorescence resonance energy transfer (FRET) to determine whether IL-17RA subunits multimerize, and, if so, whether they are preassembled in the plasma membrane [6].
• We demonstrate here that IL-17 receptor family shares sequence homology in their intracellular region with Toll-IL-1 receptor (TIR) domains and with Act1, a novel adaptor previously reported as an NF-kappaB activator [7].
• Based on sequence and functional similarities, this novel IL-17 receptor homologue represents a potential human SEF and is likely to play critical roles in endothelial or epithelial functions such as proliferation, migration, and angiogenesis [8].

Biological context of IL17RA

• The hIL-17R gene was localized to chromosome 22 [9].
• The predicted amino acid sequence of the hIL-17R is 69% identical to the mIL-17R, shares no homology with previously identified cytokine receptor families, and exhibits a broad tissue distribution [9].
• Using nucleic acid hybridization techniques, a cDNA encoding a human homologue of the mIL-17R (hIL-17R) was isolated from a human T cell library [9].
• BACKGROUND: Blocking the action of interleukin (IL) 17 with an IL-17 receptor (R):Fc fusion protein inhibits T-cell proliferative responses to alloantigens and prolongs vascularized heart graft survival [10].

Anatomical context of IL17RA

• Monoclonal antibodies (mAbs) generated against the hIL-17R were able to block the IL-17-induced production of cytokine from human foreskin fibroblast (HFF) cells [9].
• PROBLEM: As there has been a study in mice showing the expression of IL-17 by decidual cells and the status of IL-17 receptor expression in human pregnancy is not known, we hypothesized that IL-17 may regulate human trophoblast proliferation and invasion [11].
• Normal human keratinocytes were found to express constitutively the IL-17 receptor gene [12].
• The lack of IL-17 responsiveness in mouse stromal cells genetically deficient in IL-17RA is poorly complemented by human IL-17RA, suggesting the presence of an obligate ancillary component whose activity is species specific [13].
• Vascular endothelial cells mainly expressed IL-17R [2].

Physical interactions of IL17RA

• Binding studies suggest that recombinant hIL-17 binds to the hIL-17R with low affinity [9].

Other interactions of IL17RA

• Expression, modulation and signalling of IL-17 receptor in fibroblast-like synoviocytes of patients with rheumatoid arthritis [14].
• Immunohistochemitry and reverse transcriptase polymerase chain reaction techniques were used to identify IL-17 receptor protein and mRNA, respectively [11].
• INTRODUCTION AND OBJECTIVES: To investigate factors involved in inflammation of the prostate besides IL-15, we screened prostatic cells and tissues for IL-17 and IL-17 receptor expression [15].

Analytical, diagnostic and therapeutic context of IL17RA

• Immunohistochemistry was used to localize both IL-17 and IL-17 receptor [15].
• The expression of IL-17 receptor (R) was analyzed by Northern blot and a binding assay using 125I-labeled IL-17 [16].

References