The Histone H3 Lysine 9 Methylation Abnormal Lever And Its Mechanism In CD4+ T Lymphocytes Of Latent Autoimmune Diabetes In Adults

Part One.The Reduction of Histone H3 Lysine 9 Methylation and Its significance in CD4+ T Lymphocytes of Latent Autoimmune Diabetes in AdultsObjective:Latent autoimmune diabetes in adults(LADA)is an autoimmune disease of which the mechanism is unclear.Emerging evidence suggests that histone methylation contributes to diabetes and autoimmunity.The aim of this study was to investigate the role of histone methylation in the pathogenesis of latent autoimmune diabetes in adults.Methods:Blood from 26 LADA patients and 26 healthy controls were collected and CD4+ T lymphocytes were isolated with flow cytometry,then histone H3 lysine 9 and H3 lysine 4 methylation status was detected according to the instructions of the EpiQuik global histone H3 lysine 9 and H3 lysine 4 methylation assay kits.Results:Compared to healthy controls,reduced global H3 lysine 9 methylation was observed in CD4+ T lymphocytes of LADA patients(P<0.05).H3 lysine 4 methylation status was not statistically different(P>0.05).The reduced H3 lysine 9 methylation was correlated with GADA titer but not associated with glycosylated hemoglobin Ale.When the LADA patients group were divided into those with complication and those without complication,relatively reduced global H3 lysine 9 methylation was observed in LADA patients with complication(P<0.05).Conclusion:The reduction of histone H3 lysine 9 methylation was found in LADA patients' CD4+ T lymphocytes and this maybe a new mechanism of the pathogenesis of LADA.Part Two The Mechanism of Abnormal Histone H3 Lysine 9 Methylation Lever in CD4+ T Lymphocytes of Latent Autoimmune Diabetes in AdultsObjective:Our research suggested the histone H3 lysine 9 methylation model was abnormal in CD4+ T lymphocytes of latent autoimmune diabetes in adults(LADA),the aim of this study was to investigate the possible mechanism of the change of histone methylation in LADA.Methods:Blood from 26 LADA patients and 26 healthy controls were collected and CD4+ T lymphocytes were isolated with flow cytometry,then extacted RNA of CD4+ T lymphocytes and the mRNA expression of histone methyltransferases and demethylases were detected with RT-PCR.Results:The mRNA expression of histone methyltransferase SUV39H2 which made H3 lysine 9 methylation was downregulated in CD4+T lymphocytes of LADA patients,and the mRNA expression of histone demethylase KDM4C for H3 lysine 9 demethylation was upregulated.Conclusion:The downregulation of methyltransferase SUV39H2 and the upregulation of demethylase KDM4C was found in LADA patients' CD4+ T lymphocytes.And this maybe the mechaniasm of abnormal histone H3 lysine 9 methylation lever of LADA patients.Part Three The Histone H3 Lysine 9 Methylation Lever of Foxp3 and IL-12 Promotor in CD4+ T Lymphocytes of Latent Autoimmune Diabetes in AdultsObjective:The aim of this study was to investigate the histone H3 lysine 9 methylation lever of Foxp3 and IL-12 promotor in CD4+ T lymphocytes of LADA patients.Methods:Blood from 3 LADA patients and 3 healthy controls were collected and CD4+ T lymphocytes were isolated with flow cytometry,then the H3K9 methylation lever of Foxp3 and IL-12 promotor were detected with CHIP and RT-PCR.Results:The H3K9 methylation lever of IL-12 promotor was downregulated in CD4+T lymphocytes of LAD A patients,the H3K9 methylation lever of Foxp3 promotor had no difference between LADA patients and healthy controls.Conclusion:The decreased H3K9 methylation lever of IL-12 promotor was found in CD4+T lymphocytes of LADA patients.Total conclusion:The reduction of histone H3 lysine 9 methylation was found in LADA patients' CD4+ T lymphocytes and this maybe a new mechanism of the pathogenesis of LADA.The downregulation of methyltransferase SUV39H2 and the upregulation of demethylase KDM4C was found in LADA patients' CD4+ T lymphocytes.And this maybe the mechaniasm of abnormal histone H3 lysine 9 methylation lever of LADA patients.The decreased H3K9 methylation lever of IL-12 promotor was found in CD4+T lymphocytes of LADA patients.