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Hypoxia-induced PD-L1/PD-1 crosstalk impairs T-cell function in sleep apnoea

Authors :
Ramon Farré
Isaac Almendros
Aníbal Varela-Serrano
Raquel Casitas
Isabel Fernández-Navarro
Enrique Hernández-Jiménez
Francisco García-Río
Carolina Cubillos-Zapata
Eduardo López-Collazo
Aldara García-Sánchez
Luis A. Aguirre
José Avendaño-Ortiz
Marta Torres
Victor Toledano
Jose Casas-Martin
Source :
European Respiratory Journal. 50:1700833
Publication Year :
2017
Publisher :
European Respiratory Society (ERS), 2017.

Abstract

Obstructive sleep apnoea (OSA) is associated with higher cancer incidence, tumour aggressiveness and cancer mortality, as well as greater severity of infections, which have been attributed to an immune deregulation. We studied the expression of programmed cell death (PD)-1 receptor and its ligand (PD-L1) on immune cells from patients with OSA, and its consequences on immune-suppressing activity. We report that PD-L1 was overexpressed on monocytes and PD-1 was overexpressed on CD8+ T-cells in a severity-dependent manner. PD-L1 and PD-1 overexpression were induced in both the human in vitro and murine models of intermittent hypoxia, as well as by hypoxia-inducible factor-1α transfection. PD-L1/PD-1 crosstalk suppressed T-cell proliferation and activation of autologous T-lymphocytes and impaired the cytotoxic activity of CD8+ T-cells. In addition, monocytes from patients with OSA exhibited high levels of retinoic acid related orphan receptor, which might explain the differentiation of myeloid-derived suppressor cells. Intermittent hypoxia upregulated the PD-L1/PD-1 crosstalk in patients with OSA, resulting in a reduction in CD8+ T-cell activation and cytotoxicity, providing biological plausibility to the increased incidence and aggressiveness of cancer and the higher risk of infections described in these patients.

Details

ISSN :
13993003 and 09031936
Volume :
50
Database :
OpenAIRE
Journal :
European Respiratory Journal
Accession number :
edsair.doi.dedup.....2c526d368dd6da387be0cc09e138cf65
Full Text :
https://doi.org/10.1183/13993003.00833-2017