Dendritic cell subsets in autoimmune diabetes

我们正在确定NOD小鼠与非自身免疫品系的dc差异，以及NOD小鼠在不同糖尿病发病状态和疾病部位的dc差异。我们关注的是糖尿病前期，此时致病信号和调控信号相互竞争。我们比较了NOD和对照组B6小鼠在先天刺激和非先天刺激下的DC亚群基因表达，并确定了NOD DC在细胞因子和共刺激反应方面的差异。我们还发现，尽管ifn - α和ifn - β的产生较高，但CpG刺激后NOD dc中1型ifn应答基因的诱导较少。在NOD dc中，ifn - α刺激后，典型ifn - α受体信号通路受损，包括活化STAT1的核定位降低。

We are determining how DCs differ in NOD mice compared to non-autoimmune strains, and how DCs are different in NOD mice at different diabetes pathogenesis states and disease sites. We have focused on the prediabetic phase when both pathogenic and regulatory signals are competing. We compared gene expression of sorted DC subsets from NOD and control B6 mice with and without innate stimulation, and have identified differences in the cytokine and costimulatory responses of NOD DCs. We also find that, despite higher IFN-alpha and IFN-beta production, type 1 IFN-responsive genes are induced less in NOD DCs after CpG stimulation. Canonical IFN-alpha receptor signaling is impaired after IFN-alpha stimulation in NOD DCs, including decreased nuclear localization of activated STAT1.