The Relationship Between The Changes Of 7α,25-OHC/GPR183 Signal Axis And The Pathogenesis And The Rate Of Disease Progression Of Parkinson’s Disease

Objective:At present,more and more studies show that Parkinson’s disease(PD)is a kind of autoimmune-mediated disease.Besides the central immunity mediated by microglia cells,the disorder of peripheral immune cell population and the central migration and infiltration of peripheral immune cells are also important factors for the onset and progression of PD.Recent studies have shown that changes in the 7a,25-OHC-GPR183 signaling axis are involved in the proliferation and migration of peripheral T lymphocytes in patients with multiple sclerosis,suggesting that changes in the signaling axis may be involved in immune-mediated peripheral immune disorders,as a potential peripheral immune regulatory network.However,whether this signal axis is involved in peripheral immune disorder in PD patients remains unclear.Therefore,by collecting clinical data of PD patients and using ELISA and cytometry,this study intended to study the changes of peripheral blood immune cell subsets and the signal axis of 7α,25-OHC-GPR183 in PD patients,and analyze the correlation between the above changes and the severity of PD disease,in order to provide clinical clues for finding new targets of peripheral immune regulation in PD.Methods:Thirty PD patients and thirty controls who were hospitalized in the Department of Neurology from April 1,2022 to October 31,2022 were selected.Demographic data of all subjects were collected.H-Y stage and Unified Parkinson’s Disease Rating Scale were used to assess the severity of motor symptoms in PD patients.MMSE and MOCA were used to assess cognitive function in PD patients.Peripheral blood inflammatory cells were detected by blood cell count.ELISA was used to detect GPR183 ligand 7α,25-OHC producing enzyme CH25H,CYP7B1 and degrading enzyme HSD3B7.Flow cytometry was used to detect the percentage of T lymphocyte subsets and GPR183 expression in peripheral blood.The differences and correlations of above indicators were analyzed.Results:1.Compared with the normal group,the total number of lymphocytes(t=-3.176,P=0.002),the total number of T lymphocytes(t=-2.214,P=0.031),the granulocyte to lymphocyte ratio(z=-2.898,P=0.004),the granulocyte to monocyte ratio(z=-2.499,P=0.012)in the PD group were significantly higher than those in the normal group.No significant differences were found in T lymphocyte subsets(total T,CD4+T,CD8+T,Th1,Th2,Th17,Th1/Th2,CD4+/CD8+ ratio)between the two groups(P≤0.05).2.GPR183 receptor was expressed on CD4+T,CD8+T,Th1,Th2 and Th17 lymphocytes.In PD patients,The expression level of GPR183 receptor on Th1 cells was correlated with disease duration(r=0.583,P=0.001),the annual rate of change of HY stage(r=-0.528,P=0.003),UPDRS total score(r=-0.445,P=0.014),UPDRSI(r=-0.466,P=0.009),UPDRSⅡ(r=-0.397,P=0.030)and UPDRSⅢ(r=-0.482,P=0.007).After adjusting for the influence of age,the correlation between the above indicators still existed.3.The level of GPR183 receptor in Th1 cells was correlated with the level of IL-1β in peripheral blood(r=-0.413,P=0.026),but not with other cytokines(P>0.05).4.The expression levels of GPR183 ligand 7α,25-OHC synthase CH25H(z=-2.516,P=0.012)and CYP7B1(z=-2.374,P=0.018)in PD group were significantly higher than those in control group.The expression level of HSD3B7 was significantly lower than that of the control group(z=-3.088,P=0.002).Conclusion:PD patients have disorder of the 7α,25-OHC/GPR183 signaling axis,which is related to the course of disease and the rate of disease progression.This study provides a new idea for finding a peripheral intervention target for PD.