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Retroviral CRISPR/Cas9-Mediated Gene Targeting for the Study of Th17 Differentiation in Vitro
Published on: November 15, 2024
Cutting edge: interleukin 17 signals through a heteromeric receptor complex
Dean Toy1, David Kugler, Martin Wolfson
1Department of Inflammation, Amgen, 1201 Amgen Court West, Seattle, WA 98119, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|June 21, 2006
Summary
Interleukin-17 (IL-17) signaling requires both IL-17RA and IL-17RC receptor components. This discovery reveals a new paradigm for IL-17 interactions in autoimmune diseases.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Interleukin-17 (IL-17) is a key inflammatory cytokine produced by CD4 T cells, implicated in autoimmune disease pathogenesis.
- The IL-17 receptor subunit alpha (IL-17RA) is crucial for IL-17's biological activity, mediating its effects on stromal cells.
- Species-specific differences in IL-17 responsiveness suggest additional receptor components beyond IL-17RA.
Purpose of the Study:
- To identify the species-specific ancillary component involved in IL-17 receptor signaling.
- To elucidate the complete receptor complex required for IL-17 biological activity.
- To propose a new model for IL-17 ligand-receptor interactions.
Main Methods:
- Investigating IL-17 responsiveness in mouse stromal cells lacking IL-17RA.
- Assessing the complementation of IL-17 signaling by human IL-17RA.
- Identifying the novel IL-17 receptor component through functional assays.
Main Results:
- Mouse stromal cells deficient in IL-17RA showed limited response to IL-17, even with human IL-17RA expression.
- The novel component, IL-17 receptor subunit gamma (IL-17RC), was identified as essential for IL-17 signaling.
- IL-17 biological activity is dependent on a functional complex of IL-17RA and IL-17RC.
Conclusions:
- The IL-17 receptor complex comprises both IL-17RA and IL-17RC.
- IL-17RC is a critical, species-specific ancillary component for IL-17 signaling.
- This finding establishes a new paradigm for understanding IL-17 family interactions and their role in immunity and disease.
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