TY - JOUR
T1 - Expression and Regulation of Siglec-6 (CD327) on Human Mast Cells and Basophils
AU - Smiljkovic, Dubravka
AU - Herrmann, Harald
AU - Sadovnik, Irina
AU - Gamperl, Susanne
AU - Berger, Daniela
AU - Stefanzl, Gabriele
AU - Eisenwort, Gregor
AU - Hoermann, Gregor
AU - Kopanja, Sonja
AU - Dorofeeva, Yulia
AU - Focke-Tejkl, Margarete
AU - Jaksch, Peter
AU - Hoetzenecker, Konrad
AU - Szepfalusi, Zsolt
AU - Valenta, Rudolf
AU - Arock, Michel
AU - Valent, Peter
N1 - Funding Information:
This study was supported by the Austrian Science Fund (FWF), grants DK W1248-B30, P32470-B, and F4704-B20 to P.V., grant DK W1248-B13 to Z.S., and the Danube Allergy Research Cluste r of the Country of Lower Austria to R.V. The funders played no role in study design, data collection and analysis, decision to publish, or preparation of the report.
Funding Information:
This study was supported by the Austrian Science Fund (FWF), grants DK W1248-B30, P32470-B, and F4704-B20 to P.V., grant DK W1248-B13 to Z.S., and the Danube Allergy Research Cluster of the Country of Lower Austria to R.V. The funders played no role in study design, data collection and analysis, decision to publish, or preparation of the report.
Publisher Copyright:
© 2022 The Authors
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
KW - Allergy
KW - C5a
KW - IL-3
KW - IgE
KW - Siglec-6
KW - basophils
KW - mast cells
KW - mastocytosis
UR - http://www.scopus.com/inward/record.url?scp=85137119751&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2022.07.018
DO - 10.1016/j.jaci.2022.07.018
M3 - Journal article
C2 - 35953001
SN - 0091-6749
VL - 151
SP - 202
EP - 211
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 1
ER -