Expression and Regulation of Siglec-6 (CD327) on Human Mast Cells and Basophils

Dubravka Smiljkovic, Harald Herrmann, Irina Sadovnik, Susanne Gamperl, Daniela Berger, Gabriele Stefanzl, Gregor Eisenwort, Gregor Hoermann, Sonja Kopanja, Yulia Dorofeeva, Margarete Focke-Tejkl, Peter Jaksch, Konrad Hoetzenecker, Zsolt Szepfalusi, Rudolf Valenta, Michel Arock, Peter Valent

Research output: Journal article (peer-reviewed)Journal article

1 Citation (Scopus)

Abstract

BACKGROUND: Mast cells and basophils are effector cells of allergic reactions and display a number of activation-linked cell surface antigens. Of these antigens, however, only a few are functionally relevant and specifically expressed in these cells.

OBJECTIVE: To identify mast cell- and basophil-specific surface molecules and to study their cellular distribution and regulation during cytokine-induced and IgE-dependent activation.

METHODS: Multi-color flow cytometry was performed to recognize surface antigens and to determine changes in antigen expression upon activation.

RESULTS: We identified Siglec-6 (CD327) as a differentially regulated surface antigen on human mast cells and basophils. In the bone marrow, Siglec-6 was expressed abundantly on mast cells in patients with mastocytosis and in reactive states, but was not detected on other myeloid cells, with the exception of basophils and monocytes. In healthy individuals, allergic patients, and patients with chronic myeloid leukemia (CML), Siglec-6 was identified on CD203c+ blood basophils, a subset of CD19+ B lymphocytes and few CD14+ monocytes, but not on other blood leukocytes. CML basophils expressed higher levels of Siglec-6 than normal basophils. Interleukin-3 (IL-3) promoted Siglec-6 expression on normal and CML basophils, and stem cell factor (SCF) increased the expression of Siglec-6 on tissue mast cells. Unexpectedly, IgE-dependent activation resulted in downregulation of Siglec-6 in IL-3-primed basophils whereas in mast cells, IgE-dependent activation augmented SCF-induced upregulation of Siglec-6.

CONCLUSIONS: Siglec-6 is a dynamically regulated marker of mast cells and basophils. Activated mast cells and basophils exhibit unique ´Siglec-6-responses´, including cytokine-dependent upregulation and unique differential, cell-specific responses to IgE-receptor cross-linking.

Original languageEnglish
Pages (from-to)202-211
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Volume151
Issue number1
Early online date8 Aug 2022
DOIs
Publication statusPublished - Jan 2023

Keywords

  • Allergy
  • C5a
  • IL-3
  • IgE
  • Siglec-6
  • basophils
  • mast cells
  • mastocytosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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