Expression Of Peli1 In Autoimmune Premature Ovarian Insufficiency And Its Effects On The Biological Characteristics Of Treg

OBJECTIVEPremature ovarian insufficiency(POI)is a common disease in the gynecological endocrine field,and immune abnormalities are common causes of pathogenesis.The antigenic targets and autoantibodies of POI have not been fully clarified,and the specific pathogenesis needs to be further studied.T regulatory cells(Treg)has the ability of maintaining immune balance and limiting excessive immunity.In autoimmune POI,Treg and cytokines IL-10 and TGF-β1 decreased,indicating that Treg and its cytokines IL-10 and TGF-β1 are involved in the development of autoimmune POI.Pelil negatively regulates the activation of T lymphocytes,participates in regulating the proliferation and activation of immune cells,and participates in the occurrence of various autoimmune diseases.However,whether Pelil is involved in the pathogenesis of autoimmune POI or whether Pelil has regulatory effect on Treg has not been reported.Therefore,this project intends to study the expression of Pelil in autoimmune POI,explore the effect of Pelil on the biological characteristics of spleen Treg cells,and provide theoretical basis for further exploring the pathogenesis and subsequent treatment of autoimmune POI.Chapterl Expression of Pelil in PBMC and Spleen Treg cells of Autoimmune POIMETHODSTo explore the expression of Peli1 in Autoimmune POI mouse model.Autoimmune POI mouse model were constructed by zona pellucida 3 peptides.Isolating peripheral blood mononuclear cells(PBMC)and spleen Treg cells from mice,and detecting the expression of Pelil in PBMC and Treg.RESULTS1.Compared with the normal group,the model group had lower serum E2 and AMH,higher serum FSH,smaller follicle counts at all levels of ovaries,lower IL-10 and higher IFN-y in ovarian homogenates,indicating that the autoimmune POI mouse model was successfully constructed.2.Compared with the normal group,the expression levels of Pelil mRNA and protein in PBMC and spleen Treg were decreased in autoimmune POI mouse model.Chapter2 Expression of Pelil in PBMC of Patients with Autoimmune POI METHODSTo explore the expression of Pelil in patients with autoimmune POI.Collecting peripheral blood from patients with autoimmune POI and isolate PBMC,detecting the expression of Peli1 in PBMC.RESULTS1.Compared with the normal group,women with autoimmune POI had lower serum E2 and AMH,higher serum FSH and LH.84.6%of the autoimmune POI patients had at least two immune indicators.2.Compared with the normal group,the levels of Pelil mRNA and protein in PBMC were decreased in patients with autoimmune POI.Chapter3 Effects of Pelil on Treg CellsMETHODSTo explore the effects of Pelil on the biological characteristics of Tregs.Constructing lentivirus vector and transfecting mouse spleen Tregs.Detecting the proliferation rate,apoptosis rate,and immunosuppressive functions of Treg cells.RESULTS1.The lentiviral vector LV-Pelil was successfully constructed.After transfection,the expression level of Pelil in Treg was increased in the normal upregulation group and the model upregulation group.2.Compared with the normal blank group and normal no-load group,the Treg cells in the normal upregulation group had increased proliferation rates,decreased apoptosis rates,increased immunosuppressive functions,and higher levels of IL-10 and TGF-β in cell culture.3.Compared with the model blank group and model unloaded group,the Treg cells in the model upregulation group had increased proliferation rates,decreased apoptosis rates,increased immunosuppressive functions,and higher levels of IL-10 and TGF-β in cell culture.CONCLUSIONS1.The expression of Pelil in PBMC and spleen Treg were decreased in autoimmune POI mouse model.2.The expression of Pelil in PBMC was decreased in autoimmune POI women.3.Overexpression of Peli1 can promote the proliferation of Treg cells,inhibit Treg apoptosis and enhance its immunosuppressive function.