Galectin 7 leads to a relative reduction in CD4+ T cells, mediated by PD-1

Area of Science:

• Immunology
• Glycobiology
• Cancer Research

Background:

• Glycan-binding proteins are increasingly recognized for their role in modulating immune responses.
• Immune regulatory receptors, such as PD-1, are crucial targets in cancer immunotherapy.
• The specific mechanisms by which galectins interact with immune checkpoints are not fully understood.

Purpose of the Study:

• To investigate the role of galectin 7 in regulating CD4+ T cell populations.
• To elucidate the interaction between galectin 7 and the programmed cell death protein 1 (PD-1) receptor.
• To explore the functional consequences of galectin 7 binding to PD-1 glycosylation sites.

Main Methods:

• In vitro cell culture and mouse tumor models were used to assess CD4+ T cell percentages.
• Immunohistochemical staining of esophageal cancer patient samples analyzed galectin 7 and CD4+ cell co-localization.
• Binding assays, PD-1 knockout mouse models, and siRNA-mediated PD-1 inhibition were employed to study the galectin 7-PD-1 interaction.
• SHP-2 recruitment and NFAT activity were assessed following galectin 7 treatment.

Main Results:

• Galectin 7 significantly reduced CD4+ T cell percentages in vitro and in vivo.
• Lower CD4+ T cell counts correlated with high galectin 7 expression in esophageal cancer tissues.
• Galectin 7 binding to PD-1 N-glycosylation sites (N74, N116) was confirmed, leading to SHP-2 recruitment.
• Inhibition of PD-1 or SHP-2 abrogated galectin 7's NFAT suppressive activity.

Conclusions:

• Galectin 7 acts as an inhibitor of CD4+ T cell function, potentially through its interaction with PD-1.
• The N-glycosylation of PD-1 is critical for galectin 7 binding and subsequent immune modulation.
• This study reveals a novel mechanism of immune regulation involving galectin 7 and PD-1 glycosylation, suggesting potential therapeutic strategies.