The Role And Mechanism Of Th17 And MDSC In The Progression Of Parkinson's Disease

Objective:Through the detection and correlation analysis of T helper 17 cells(Th17)and Myeloid-derived suppressor cells(MDSC)in newly diagnosed Parkinson's disease(PD)patients and PD mouse model,the expressions of Th17 and MDSC are explored and the mechanism of the two cells in the pathogenesis of PD is elaborated.Methods:1.The clinical data of 32 PD patients who had not been treated with anti-PD therapy were collected as the PD group,and the healthy volunteers with the same age were enrolled as the control group.The severity of PD patients was evaluated by Hoehn and Yahr classification and Unified Parkinson Disease Rating Scale.Flow cytometry was used to detect the percentage of Th17 and MDSC in the peripheral blood.The correlations among Th17,MDSC and the severity of PD were analyzed.2.Forty C57BL/6 mice were randomly divided into PD group,PD + gemcitabine group,gemcitabine group and control group.Mice in PD group and PD + gemcitabine group were injected with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)to establish PD model.Mice in PD + gemcitabine group and gemcitabine group were injected intraperitoneally with gemcitabine.Mice in control group were injected with the equal amounts of normal saline.The PD mice model was evaluated by the general movement of mice(tremor,movement,gait,hair,etc.),behavioral experiments(pole climbing test,suspension test,forced swimming test),and tyrosine hydroxylase(TH)positive cells were detected by immunohistochemistry.Flow cytometry was used to detect the percentage of Th17 and MDSC in the spleen suspension of mice.The correlation between Th17 and MDSC was analyzed.Results:1.The percentage of Th17 and MDSC in peripheral blood of PD patients was significantly higher than that in control group,and two cells in PD group were positively correlated.The results were significant differences.There was no correlation between the severity of PD and Th17 or MDSC in PD group.2.PD mice established by MPTP showed the loss of motor ability and abnormal motor behavior.Compared with mice in gemcitabine group and control group,turning around time,pole climbing time and rest time of mice in PD group and PD + gemcitabine group were longer in the pole climbing experiment and forced swimming test,suspension time of mice in PD group and PD + gemcitabine group was reduced in the suspension test.The number of TH cells in the substantia nigra of PD group and PD + gemcitabine group was decreased compared with that in the gemcitabine group and the control group.The results were significant differences.3.The percentage of Th17 in the spleen suspension of mice in PD group was higher than that in gemcitabine group and control group.The percentage of Th17 in the spleen suspension of mice in PD + gemcitabine group was higher than that in the other three groups.The results were significant differences.There was no significant difference between gemcitabine group and control group.4.The percentage of MDSC in the spleen suspension of mice in PD group was higher than that in the other three groups.The percentage of MDSC in the spleen suspension of mice in PD + gemcitabine group was higher than that in gemcitabine group and control group.The results were significant differences.There was no significant difference between gemcitabine group and control group.5.There was no correlation between Th17 and MDSC in the spleen suspension of mice in the PD group and PD + gemcitabine group.Conclusions:1.There is neuroinflammation in Parkinson's disease,with Th17 and MDSC involved in the mechanism.2.The expression of Th17 and MDSC in peripheral blood of newly diagnosed PD patients was significantly higher than that in healthy controls.3.The PD model was successfully established in this study,and gemcitabine in the PD model did not have a significant impact on PD pathology and symptoms.4.The expression of Th17 and MDS0 C in the spleen suspension of PD mouse model was significantly higher than that in normal mice.5.Th17 and MDSC may participate in and promote the development of PD neuroinflammation reaction.6.In the subacute PD mouse model established by MPTP,MDSC can exert its immunomodulatory effect to inhibit Th17 amplification.