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The glycoimmune checkpoint receptor Siglec-7 interacts with T-cell ligands and regulates T-cell activation.
Stewart, Natalie; Daly, John; Drummond-Guy, Olivia; Krishnamoorthy, Vignesh; Stark, Jessica C; Riley, Nicholas M; Williams, Karla C; Bertozzi, Carolyn R; Wisnovsky, Simon.
Afiliación
  • Stewart N; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
  • Daly J; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
  • Drummond-Guy O; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
  • Krishnamoorthy V; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
  • Stark JC; Department of Chemistry & Sarafan ChEM-H, Stanford University, Stanford, California, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Boston, Massachusetts, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Boston, Massachusetts, USA
  • Riley NM; Department of Chemistry & Sarafan ChEM-H, Stanford University, Stanford, California, USA; Department of Chemistry, University of Washington, Seattle, Washington, USA.
  • Williams KC; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
  • Bertozzi CR; Department of Chemistry & Sarafan ChEM-H, Stanford University, Stanford, California, USA; Howard Hughes Medical Institute, Stanford, California, USA.
  • Wisnovsky S; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: simon.wisnovsky@ubc.ca.
J Biol Chem ; 300(2): 105579, 2024 Feb.
Article en En | MEDLINE | ID: mdl-38141764
ABSTRACT
Siglec-7 (sialic acid-binding immunoglobulin-like lectin 7) is a glycan-binding immune receptor that is emerging as a significant target of interest for cancer immunotherapy. The physiological ligands that bind Siglec-7, however, remain incompletely defined. In this study, we characterized the expression of Siglec-7 ligands on peripheral immune cell subsets and assessed whether Siglec-7 functionally regulates interactions between immune cells. We found that disialyl core 1 O-glycans are the major immune ligands for Siglec-7 and that these ligands are particularly highly expressed on naïve T-cells. Densely glycosylated sialomucins are the primary carriers of these glycans, in particular a glycoform of the cell-surface marker CD43. Biosynthesis of Siglec-7-binding glycans is dynamically controlled on different immune cell subsets through a genetic circuit involving the glycosyltransferase GCNT1. Siglec-7 blockade was found to increase activation of both primary T-cells and antigen-presenting dendritic cells in vitro, indicating that Siglec-7 binds T-cell glycans to regulate intraimmune signaling. Finally, we present evidence that Siglec-7 directly activates signaling pathways in T-cells, suggesting a new biological function for this receptor. These studies conclusively demonstrate the existence of a novel Siglec-7-mediated signaling axis that physiologically regulates T-cell activity. Going forward, our findings have significant implications for the design and implementation of therapies targeting immunoregulatory Siglec receptors.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Activación de Linfocitos / Linfocitos T / Antígenos de Diferenciación Mielomonocítica / Ligandos Límite: Humans Idioma: En Revista: J Biol Chem Año: 2024 Tipo del documento: Article País de afiliación: Canadá

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Activación de Linfocitos / Linfocitos T / Antígenos de Diferenciación Mielomonocítica / Ligandos Límite: Humans Idioma: En Revista: J Biol Chem Año: 2024 Tipo del documento: Article País de afiliación: Canadá