IL17RB Human
Description
Molecular Structure and Function
IL17RB is encoded by the IL17RB gene on human chromosome 3 and belongs to the IL-17 receptor family . Structurally, it comprises:
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Extracellular domain: 275 amino acids with conserved cysteine residues critical for ligand binding .
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Transmembrane domain: 21 amino acids anchoring the receptor to the cell membrane .
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Cytoplasmic domain: 189 amino acids involved in downstream signaling .
Recombinant human IL17RB Fc chimera proteins (e.g., CF 1207-BR) are used in research to study receptor-ligand interactions .
Ligand Binding and Signaling Pathways
IL17RB binds IL-17B and IL-25 with distinct affinities (Table 1) . Binding activates canonical pathways:
| Ligand | Binding Affinity (Kd) | Receptor Subunits | Function |
|---|---|---|---|
| IL-17B | ~30-fold weaker than IL-25 | IL17RB + IL17RA | Anti-inflammatory in colon |
| IL-25 | Higher affinity | IL17RB + IL17RA | Pro-inflammatory in colon |
Signaling mechanisms:
Role in Immune Regulation
IL17RB is expressed in mucosal tissues (e.g., colon, lung) and regulates immune responses:
Anti-Inflammatory Effects
Pro-Inflammatory Effects
Clinical Implications in Oncology
IL17RB is implicated in cancer stem cell (CSC) maintenance and metastasis (Table 2) :
Mechanisms:
Research Challenges and Future Directions
Product Specs
Sf9, Baculovirus cells.
Q&A
Here’s a structured collection of FAQs tailored for academic researchers studying human IL17RB, incorporating methodological guidance and data-driven insights:
What is the structural and functional characterization of IL17RB?
IL17RB (Interleukin-17 Receptor B) is a type I transmembrane protein with a 275-amino acid extracellular domain, a 21-residue transmembrane region, and a 189-residue cytoplasmic tail . It binds IL-17B and IL-17E (IL-25) but not IL-17A/C/F . Key methods for characterization include:
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Ligand-binding assays: Co-immunoprecipitation and surface plasmon resonance to confirm binding specificity .
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Domain mapping: Truncation mutants to identify critical regions for signaling (e.g., SEFIR domain in the cytoplasmic tail) .
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Expression profiling: Northern blot and qPCR to assess tissue distribution (high in kidney/liver; low in brain/testes) .
How is IL17RB detected in experimental systems?
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Antibody-based detection: Use anti-human IL17RB monoclonal antibodies (e.g., MAB1207 for Western blot, FAB1207P for flow cytometry) .
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siRNA knockdown: Transfect cells with siRNA targeting IL17RB (e.g., Silencer Select s7269) to validate functional roles .
What are validated cellular models for IL17RB studies?
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Primary immune cells: CD4+ T/NKT cells isolated from spleens (BALB/c mice) for IL-25/IL-17B response assays .
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Epithelial lines: AGS gastric cells for H. pylori-IL17RB interaction studies (e.g., cagA-dependent IL17RB downregulation) .
How does IL17RB signaling diverge between IL-17B and IL-17E?
IL-17E activates NF-κB and STAT3 via IL17RB/IL17RA heterodimers, while IL-17B signals through IL17RB/IL17RA but with weaker affinity . Key methodologies:
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Reporter assays: Transfect HEK293 cells with NF-κB-luciferase and IL17RB/IL17RA plasmids .
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Cytokine profiling: Measure IL-8, IL-13, or IL-5 secretion in supernatants via ELISA .
| Ligand | Receptor Complex | Key Downstream Effectors |
|---|---|---|
| IL-17E | IL17RB + IL17RA | NF-κB, STAT3, IL-8 |
| IL-17B | IL17RB + IL17RA | NF-κB (weak), CCL20 |
How to resolve contradictions in IL17RB’s role in inflammation?
IL17RB exhibits context-dependent pro- and anti-inflammatory effects:
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Pro-inflammatory: IL-17B/IL-17E drive type 2 immunity in NKT cells (e.g., IL-13 production) .
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Anti-inflammatory: H. pylori infection downregulates IL17RB in gastric mucosa, impairing CD11b+CD11c+ cell recruitment .
What strategies target IL17RB therapeutically?
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Neutralizing antibodies: D9.2 inhibits IL-17E binding (IC50: 0.5 μg/ml in CD4+ cell assays) .
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Small-molecule inhibitors: Screen compounds blocking the IL17RB SEFIR domain (e.g., FRET-based kinase assays) .
How to validate IL17RB-specific antibodies?
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Cross-reactivity testing: Compare binding to recombinant mouse IL17RB (e.g., MAB1207 shows no cross-species reactivity) .
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Functional blocking: Assess inhibition of IL-17E-induced IL-8 in HEK293-IL17RB cells (≥80% reduction = validated) .
What are pitfalls in IL17RB knockout models?
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Compensatory signaling: IL17RC upregulation in Il17rb−/− mice .
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Mitigation: Use double knockouts (e.g., Il17rb−/−/Il17rc−/−) for colitis studies.
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Microbiome confounding: Gut microbiota modulate IL17RB expression .
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Solution: Cohouse WT and KO mice pre-experiment.
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Data Contradictions & Validation
Product Science Overview
Interleukin-17 Receptor Beta (IL-17RB) is a crucial component of the immune system, playing a significant role in inflammatory and autoimmune responses. It is part of the larger interleukin-17 (IL-17) family, which includes six cytokines (IL-17A to IL-17F) that are involved in various immune functions .
IL-17RB is a type I membrane glycoprotein that binds specifically to IL-17B and IL-17E (also known as IL-25). This receptor is characterized by a shared cytoplasmic motif known as the SEF/IL-17R (SEFIR) domain . The binding of IL-17B and IL-17E to IL-17RB triggers a cascade of signaling pathways that lead to the production of proinflammatory cytokines and chemokines .
The IL-17RB pathway has been implicated in several diseases, particularly those involving inflammation and autoimmunity. For instance, IL-17RB is known to play a role in the pathogenesis of inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). Additionally, recent studies have highlighted its involvement in cancer, where it may contribute to tumor growth and metastasis .
