Siglec-7 on peripheral blood eosinophils: Surface expression and function

Fanny Legrand*, Nadine Landolina, Ilan Zaffran, Robert O. Emeh, Elizabeth Chen, Amy D. Klion, Francesca Levi-Schaffer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Background: Siglec-7 is an inhibitory receptor (IR) expressed on human blood eosinophils. Whereas activation of other IRs, including Siglec-8 and CD300a, has been shown to downregulate eosinophil function, little is known about the role of Siglec-7 on human eosinophils. Objective: To examine Siglec-7 expression and function in eosinophils from normal (ND) and eosinophilic (EO) donors. Methods: Eosinophil expression of Siglec-7 was quantified by flow cytometry and quantitative PCR. Soluble Siglec-7 (sSiglec-7) levels were measured by ELISA in serum. The effect of Siglec-7 on eosinophil viability and degranulation was assessed in vitro by AnnexinV-FITC/7-AAD staining and by measuring GM-CSF-induced mediator release in culture supernatants. Signal transduction was studied by Western blot. Results: Siglec-7 was expressed ex vivo on blood eosinophils from all eosinophilic and normal individuals studied. Siglec-7 surface, but not SIGLEC-7mRNA expression, was correlated with absolute eosinophil count (AEC). Siglec-7 was upregulated on purified eosinophils after in vitro stimulation with GM-CSF or IL-5. Serum sSiglec-7 was detectable in 133/144 subjects tested and correlated with AEC. Siglec-7 cross-linking inhibited GM-CSF-induced release of eosinophil peroxidase, TNF-α, and IL-8 (n = 7–8) but did not promote eosinophil apoptosis (n = 5). Finally, Siglec-7 cross-linking on GM-CSF-activated eosinophils induced phosphorylation of SHP-1 and de-phosphorylation of ERK1/2 and p38. Conclusions: Siglec-7 is constitutively expressed on human eosinophils and downmodulates eosinophil activation. Targeting of Siglec-7 on eosinophils might enhance treatment efficacy in eosinophil-driven disorders. Conversely, therapeutic interventions that inhibit Siglec-7 could have unanticipated consequences and promote eosinophilic inflammation.

Original languageAmerican English
Pages (from-to)1257-1265
Number of pages9
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume74
Issue number7
DOIs
StatePublished - Jul 2019

Bibliographical note

Publisher Copyright:
© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Keywords

  • ITIM
  • Siglec-7
  • Siglec-8
  • apoptosis
  • eosinophilia
  • eosinophils
  • hypereosinophilic syndrome
  • signaling

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