Study On The Regulatory Effect Of PDC/mDC On CD4~+T Cell In Primary Immune Thrombocytopenia

Objective:The pathogenesis of primary immune thrombocytopenia(ITP)is complex and diverse.In recent years,T cell immunity has become a research hotspot.In this article,we investigated the imbalance of dendritic cell subsets,the abnormal expression of Th1/Th2,Th17/Treg cells and their related cytokines and transcription factors,further analyzed the correlationship between them,so as to explore their regulatory effects on the differentiation of Th1/Th2,Th17/Treg cells.Their role in the pathogenesis of ITP is further elucidated.Methods:The study included 30 patients with a preliminary diagnosis of ITP and 20 healthy subjects.Peripheral blood was collected from all ITP patients and healthy subjects.The proportion of peripheral blood myeloid dendritic cells(mDC),plasma-like dendritic cells(pDC),Th1,Th2,Th17 and Treg cells in peripheral blood mononuclear cells was detected by flow cytometr.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of IL-12,IL-23,IFN-?,IL-4,IL-17,TGF-?in peripheral blood serum.the mRNA expression of IL-12p40,IL-12p35,IL-23p19,T-bet,GATA-3,ROR?t,Foxp3wasdetectedby RT-PCR.Results:(1)Compared with the healthy control group,in the ITP group,pDC were decreased(P=0.004),mDC had no significant change(P=0.681),pDC/mDC ratio decreased(P=0.001),IL-12 and IL-23 levels increased(P<0.001,P<0.001),the expression levels of IL-12p40 mRNA,IL-12p35 mRNA,and IL-23p19 mRNA were increased(P=0.014,P=0.043,P<0.001).(2)Compared with the healthy control group,the proportion of Th1and Th17 cells in the ITP group were increased(P=0.001,P=0.031),and the levels of IFN-?and IL-17 were increased(P=0.025,P=0.005),the expression of T-bet,ROR?t were increased(P=0.018,P<0.001);The proportion of Th2 and Treg cells were decreased(P=0.007,P<0.001),IL-4,TGF-?levels were decreased(P=0.028,P=0.042),the expression of GATA-3 was increased(P<0.001),the expression of Foxp3 was increased(P=0.587).(3)Correlation analysis:(1)The proportion of total dendritic cells was positively correlated with IL-12(r=0.526,P=0.003);IL-12 was negatively correlated with platelet count(r=-0.492,P<0.032);The IFN-?was negatively correlated with platelet count(r=-0.415,P=0.028).(2)The proportion of total dendritic cells was positively correlated with IL-23(r=0.501,P=0.005),IL-23 was positively correlated with IL-17(r=0.489,P=0.006),and IL-23 was negatively correlated with platelet count(r=-0.564,P=0.001).Conclusion:The imbalance of pDC/mDC and the increase of IL-12 and IL-23 lead to the increased differentiation of CD4~+T cells into Th1 and Th17cells,which might be the important mechanisms underlying the imbalance of Th1/Th2and Th17/Treg in ITP patients.