Myeloid-derived suppressor cells aggravate Sjögren's syndrome by inhibiting the response of Th2 cells / 医学研究生学报

ABSTRACT

Objective Changes in the number and function of myeloid-derived suppressor cells (MDSC) were reported in clinical and experimental Sjögren’s syndrome (SS), whereas the underlying mechanisms of MDSCs in SS remain to be elucidated. This study was to observe the changes in the pathologic structure and function of the submandibular gland and salivary flow in SS mice after adoptive transfer or deletion of MDSCs and explore the action mechanisms of MDSCs. Methods Ten 4-week-old non-obese diabetic (NOD) mice (without SS-like symptoms) received adoptive transfer of purified MDSCs at 1×106 per mouse (the MDSC group, n = 5) or injection of PBS (the PBS group, n = 5). Another ten 10-week-old NOD mice were injected intraperitoneally with anti-Gr1 antibodies (the anti-Gr1 group, n = 5) or commensurable Rat IgG2b isotype antibodies (the Rat IgG2b group, n = 5). At 2 weeks after treatment, we determined the salivary flow rate, examined lymphocytic infiltration in the submandibular glands, and counted the MDSCs on Th2 cells in different groups of the mice. Results Compared with the PBS group, the NOD mice of the MDSC group showed significantly reduced Th2 cells in the peripheral blood ([0.67 ± 0.13] % vs [0.16 ± 0.07] %, P < 0.05) and spleen ([0.80 ± 0.13] % vs [0.37 ± 0.04] %, P < 0.05) and salivary flow ([78.70 ± 6.80] vs [33.85 ± 11.25] µL, P < 0.05), but increased numbers of MDSCs in the peripheral blood ([1.54 ± 0.14] vs [5.47 ± 1.54] ×105, P < 0.05) and spleen ([1.09 ± 0.23] vs [4.50 ± 1.04] ×105, P < 0.05). In comparison with the Rat IgG2b group, the animals of the anti-Gr1 group exhibited remarkably decreased Th2 cells in the peripheral blood ([0.55 ±0.09] % vs [0.92 ± 0.10] %, P < 0.05) and spleen ([0.63 ± 0.08] % vs [1.10 ± 0.06] %, P < 0.05) and salivary flow ([56.48 ± 14.18] vs [121.20 ± 10.34] µL, P < 0.05), as well as decreased numbers of MDSCs in the peripheral blood ([1.53 ± 0.12] vs [0.35±0.16] ×105, P < 0.05) and spleen ([2.53 ± 1.10] vs [0.91±0.07] ×105, P < 0.05). The adoptive transfer of MDSCs aggravated while the injection of anti-Gr1 antibodies attenuated lymphocytic infiltration in the submandibular gland of the mice. Conclusion MDSCs participate in the pathogenesis Sjögren’s syndrome by suppressing the response of Th2 cells, which suggests that increasing the response of Th2 cells by inhibiting MDSCs could be a novel target for the treatment of Sjögren’s syndrome.