PSGL-1: a novel immune checkpoint driving T-cell dysfunction in obstructive sleep apnea

Front Immunol. 2023 Oct 3:14:1277551. doi: 10.3389/fimmu.2023.1277551. eCollection 2023.

Abstract

Introduction: Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Recently, the adhesion receptor P-selectin glycoprotein-1 (PSGL 1) has been identified as a novel immune checkpoint, which are recognized major hallmarks in several types of cancer and have revolutionized cancer therapy.

Methods: The expression of PSGL-1 and its ligands VISTA and SIGLEC-5 was assessed in the leucocytes of OSA patients and control subjects exploring the role of intermittent hypoxia (IH) using in vitro models. In addition, PSGL-1 impact on T-cells function was evaluated by ex vivo models.

Results: Data showed PSGL-1 expression is upregulated in the T-lymphocytes from patients with severe OSA, indicating a relevant role of hypoxemia mediated by intermittent hypoxia. Besides, results suggest an inhibitory role of PSGL-1 on T-cell proliferation capacity. Finally, the expression of SIGLEC-5 but not VISTA was increased in monocytes from OSA patients, suggesting a regulatory role of intermittent hypoxia.

Discussion: In conclusion, PSGL-1 might constitute an additional immune checkpoint leading to T-cell dysfunction in OSA patients, contributing to the disruption of immune surveillance, which might provide biological plausibility to the higher incidence and aggressiveness of several tumors in these patients.

Keywords: PSGL-1; SIGLEC-5; T-cells; VISTA; immune surveillance; immunecheckpoints; intermittent hypoxia; sleep apnea.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Hypoxia / etiology
  • Hypoxia / genetics
  • Hypoxia / immunology
  • Membrane Glycoproteins* / biosynthesis
  • Membrane Glycoproteins* / genetics
  • Membrane Glycoproteins* / immunology
  • Neoplasms / etiology
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Sialic Acid Binding Immunoglobulin-like Lectins
  • Sleep Apnea, Obstructive* / complications
  • Sleep Apnea, Obstructive* / genetics
  • Sleep Apnea, Obstructive* / immunology
  • T-Lymphocytes* / immunology
  • T-Lymphocytes* / metabolism

Substances

  • Membrane Glycoproteins
  • P-selectin ligand protein
  • Sialic Acid Binding Immunoglobulin-like Lectins
  • SIGLEC5 protein, human
  • VSIR protein, human

Grants and funding

This study was supported by Instituto de Salud Carlos III (ISCIII) through the projects PI13/01512, PI16/00201 and PI19/01612, PI22/01262, P2022/BMD-7224 to F. García-Río and CP18/00028, PI19/01363 and PI22/01257 to C. Cubillos-Zapata; and co-funded by the European Union, Ayudas Luis Alvarez 2021 FIBHULP. CL-F was supported by Investigo technician fellowship CAM.