Immune function of myeloid-derived suppressor cells and its mechanism in obstructive sleep apnea syndrome

Abstract

Objective: To investigate the immune function of myeloid-derived suppressor cells (MDSC) and its mechanism in obstructive sleep apnea syndrome (OSAS). Methods: Twenty OSAS patients who were diagnosed by polysomnography (Apnea Hyponea Index>30 events/h) from Sleep Disorders Center at First Affiliated Hospital between January 2015 and December 2016 were selected. The percent of CD14(+) low expression or lack of human leukocyte antigen DR (HLA-DR(-/low)) MDSC in the CD14(+) monocyte from both OSAS patients and healthy people were analyzed by flow cytometry. In vitro assay, MDSC from OSAS patients and health people were sorted by flow cytometry and T cells were sorted with negative isolation kit. For T-cell proliferation assays, the carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled T cells were respectively incubated with autologous MDSC. CFSE fluorescence intensity of T cells was detected by flow cytometry. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were used to evaluate the concentrations of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), IL-10, transforming growth factor-β(1) (TGF-β(1)), positive rate of programmed death ligand-L1 (PD-L1), relative transcript level of Arginase 1 (Arg1), inducible nitric oxide synthase (iNOS), hypoxic inducible factor-1α (HIF-1α) expressed by MDSC. Results: Comparing to healthy people, the percentage of CD14(+)HLA-DR(-/low) MDSC in CD14(+) monocyte was significantly elevated [(12.5±1.5)% vs (3.5±0.4)%, P<0.05]. In vitro, OSAS patient-derived MDSC exhibited a stronger suppressive effect on T-cell proliferation [(23.2±1.1)% vs (53.7±3.2)%, P<0.05]. Further analysis revealed that OSAS patient-derived MDSC secreted much higher concentrations of IL-6, TNF-α, IL-10 and TGF-β(1) [(1 316±163) vs (642±72) ng/L, (316±35) vs (167±18) ng/L, (385±42) vs (108±26) ng/L and (44 276±4 589) vs (9 557±1 124) ng/L] (all P<0.05). The percentage of membrane molecule PD-L1-positive cells in OSAS patient-derived MDSC was obviously higher than that in healthy people-derived MDSC [(75.6±7.9)% vs (30.6±2.5)%, P<0.05]. Compared with healthy people-derived MDSC, the relative transcript level of Arg1, iNOS and HIF-1α in OSAS patient-derived MDSC was also increased by (4.6±0.5), (2.8±0.3) and (4.3±0.4) fold, respectively (all P<0.05). Conclusions: OSAS may be capable of inducing the proliferation of MDSC and its expression of immunosuppressive molecules by activating HIF-1α signal, thereby enhancing the immunosuppressive ability of MDSC.