signature=3963fa64ec5f49336c10c7862cebe18c,Functional Abnormalities and Regulatory Mechanisms of Pla...

摘要：

Background and aims:Systemic lupus erythematosus(SLE)is a chronic multi-organ autoimmune disease with immunological features of a prominent"interferon(IFN)signature",which is marked by the elevated expression of type I IFNregulated genes in blood and tissue cells of patients with this condition.Plasmacytoid dendritic cells(pDCs),the most potent type I IFN-producing cells,are previously found to be hyperactive in SLE.Using the New Zealand Black/White F1 lupus mouse model,the current study sought for the regulatory mechanism of IFN production by pDCs in SLE.Methods:Mice with lupus symptoms(symptomatic)such as high titers of serum anti-nuclear antibodies and persistent proteinuria were compared with the pre-symptomatic ones.Age-and sex-matched non-lupus maternal NZW mice were used as controls.Results:While the development of pDCs appeared to be unaffected by lupus,elevated upregulation of MHC class II and co-stimulatory molecules,and induction of IFN-stimulated gene Ifitm3 in TLR7-stimulated lupus pDCs suggested phenotypic and functional hypersensitivity of these cells.Furthermore,analysis of the expression profile of microRNAs in pDCs upon TLR7 activation identified six differentially regulated targets.Among these,miR-155 was the most highly induced and its induction was consistently higher in pDCs from symptomatic NZB/W F1 mice.Conclusions:Current investigations pursue on the correlation between up-regulated miRNA-155 induction and aberrant pDC functions in SLE using miRNA mimics and inhibitors.It is hoped that findings from this study contribute to a better understanding of SLE pathogenesis and ignite future interests in evaluating the molecular layer of regulation in autoimmunity.

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