LPS induced CXCL10 chemokine production via IFN- a receptor and toll-like receptor 4 signalling

CXCL10 is a chemokine induced by IFN-? and implicated in the pathogenesis of type 1 diabetes (T1D). It attracts IFN-?-producing T cells to the pancreatic islets, forming a positive feed-forward loop where T cells induce CXCL10 and attract themselves, but it is unclear what attracts the first IFN-?-producing T cells in islets. Lipopolysaccharide induced CXCL10 production in cultured islets of nonobese diabetic (NOD) mice, and the lack of its inhibition in islets from NOD mice deficient for RAG1 or IFN-g receptor revealed its dissociation from the requirement of T cells and IFN-?. To further investigate the mechanism of LPS induced CXCL10 production, the gene expression profile of pancreatic beta cells after culture of whole islets in LPS was analysed. Overall a gene expression signature of cytokine signalling, particularly by type I IFNs and TLR4 was upregulated after culture of islets in LPS. Overall design: Islets were isolated from 6-8 week old male NOD mice and cultured for 48 hours with 50ng/ml lipopolysaccharide. Islets were then dispersed to single cells with trypsin and beta cells were sorted using FACS. RNA was isolated and subjected to RNA sequencing. There were n=5 independent samples per group, untreated and LPS-treated.