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

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-alpha (TNF-alpha), IL-10, transforming growth factor-beta(1) (TGF-beta(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-1alpha (HIF-1alpha) 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-alpha, IL-10 and TGF-beta(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-1alpha 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-1alpha signal, thereby enhancing the immunosuppressive ability of MDSC.