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Published on: May 10, 2024
SIRPα/CD172a regulates eosinophil homeostasis
Noel Verjan Garcia1, Eiji Umemoto, Yasuyuki Saito
1Laboratory of Immunodynamics, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
Journal of Immunology (Baltimore, Md. : 1950)
|July 22, 2011
Summary
Signal regulatory protein α (SIRPα) on intestinal eosinophils inhibits degranulation and promotes survival, likely via CD47 interaction. Targeting SIRPα may treat eosinophil-associated diseases.
Area of Science:
- Immunology
- Cell Biology
- Gastroenterology
Background:
- Eosinophils reside in the small intestine lamina propria but typically don't degranulate under normal conditions.
- Signal regulatory protein α (SIRPα)/CD172a is an inhibitory receptor, and CD63 is associated with degranulation.
Purpose of the Study:
- To investigate the role of SIRPα/CD172a in regulating intestinal eosinophil homeostasis and function.
- To explore the impact of SIRPα/CD172a signaling on eosinophil survival and degranulation.
Main Methods:
- Utilized novel monoclonal antibodies (mAbs) to study SIRPα/CD172a and CD63 expression on intestinal eosinophils.
- Performed cross-linking experiments on wild-type and SIRPα cytoplasmic domain-mutated (SIRPα Cyto(-/-)) mouse eosinophils.
- Analyzed eosinophil degranulation, viability, and tissue remodeling in wild-type and knockout mouse models.
Main Results:
- Intestinal eosinophils constitutively express high SIRPα/CD172a and low CD63.
- Cross-linking SIRPα/CD172a inhibited eosinophil peroxidase release; this was lost in SIRPα Cyto(-/-) eosinophils.
- SIRPα Cyto(-/-) eosinophils exhibited reduced viability, increased CD63 expression, and enhanced degranulation, with similar effects observed in CD47-deficient mice.
Conclusions:
- SIRPα/CD172a, likely through CD47 interaction, regulates intestinal eosinophil homeostasis and survival.
- Dysregulation of SIRPα/CD172a signaling contributes to increased eosinophil death and degranulation.
- SIRPα/CD172a represents a potential therapeutic target for eosinophil-related diseases.
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