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Siglec-7 on peripheral blood eosinophils: Surface expression and function
Fanny Legrand1, Nadine Landolina2, Ilan Zaffran2
1Human Eosinophil Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
Allergy
|January 29, 2019
Summary
Siglec-7 is present on human eosinophils and inhibits their activation. Targeting Siglec-7 may improve treatments for eosinophil disorders, but inhibition could worsen inflammation.
Area of Science:
- Immunology
- Cell Biology
Background:
- Siglec-7 is an inhibitory receptor on human eosinophils.
- Its role in eosinophil function is largely unknown compared to other inhibitory receptors.
Purpose of the Study:
- To investigate Siglec-7 expression and function in eosinophils from normal and eosinophilic donors.
- To understand Siglec-7's impact on eosinophil activation and signaling pathways.
Main Methods:
- Quantified Siglec-7 expression using flow cytometry and qPCR.
- Measured soluble Siglec-7 (sSiglec-7) levels via ELISA.
- Assessed Siglec-7's effect on eosinophil viability and degranulation in vitro.
- Studied signal transduction pathways using Western blot.
Main Results:
- Siglec-7 expressed on eosinophils from all donors; surface expression correlated with absolute eosinophil count (AEC).
- Siglec-7 expression increased on eosinophils stimulated with GM-CSF or IL-5.
- Cross-linking Siglec-7 inhibited GM-CSF-induced mediator release and modulated SHP-1 and ERK1/2/p38 phosphorylation, but did not induce apoptosis.
Conclusions:
- Siglec-7 is constitutively expressed on human eosinophils and downmodulates their activation.
- Targeting Siglec-7 could enhance treatment efficacy in eosinophil-driven diseases.
- Inhibiting Siglec-7 might promote eosinophilic inflammation, suggesting caution in therapeutic strategies.
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