6. participates in virus-induced pancreatic -cell inflammation by stabilizing STAT1 mRNA through interaction with the 7-Dehydrocholesterol PCBP2 protein. SNPs in lncRNAs influence disease pathogenesis and open the door to the development of diagnostic and therapeutic approaches based on lncRNA targeting. T1D is a chronic autoimmune disease in which insulin-producing pancreatic -cells are specifically destroyed by the immune system. During the initial stages of the disease, pancreatic islets are infiltrated by immune cells leading to the generation of an inflammatory environment that promotes pancreatic -cell destruction (1). Local islet inflammation MYH9 (insulitis) is partially driven by a dialog between -cells and the infiltrating immune cells, through the release of proinflammatory chemokines and cytokines by both -cells and immune cells. Increasing evidence suggests that the triggering of insulitis depends on the interaction between T1D candidate genes (2) and environmental factors, such as viral infections (3, 4). The molecular mechanisms by which viruses induce an autoimmune response targeting -cells remain unclear, however, genetically regulated host-immune response could play an important role in -cell demise through the stimulation of immune autoreactivity, first triggered and then maintained by potential persistent infections in the pancreas (3C5). Although virus-induced activation of specific transcription factors (IRF7, NFB, STAT1, and STAT2, among others) is certainly a contributory factor to gene expression changes associated with -cell failure (3, 5), recent studies indicate that a new class of gene-regulatory molecules named lncRNAs actively participate in the regulation of innate immune responses in different cell types (6, 7). LncRNAs are noncoding RNAs that are 200 nucleotides or longer in transcript length and whose structure is similar to the one of protein-coding genes (8). Several studies have implicated lncRNAs in a wide range of biological and cellular processes, including the modulation 7-Dehydrocholesterol of the innate antiviral immune response through the activation of pattern recognition receptor\related signal transduction (9), the regulation of innate immune\associated chemokines (10), and other inflammatory genes (11). LncRNAs regulate a variety of normal immune responses, but there is limited information on their implication in the development of autoimmunity, and only few lncRNAs have been identified in this context (12). Interestingly, the majority of immune disease-related genome-wide association signals map to noncoding regions of the genome, including lncRNAs. This suggests that risk variants located in lncRNAs could play regulatory roles, altering their function and leading to dysregulated expression of genes or gene networks potentially important for the development of autoimmunity. is a lncRNA located in chromosome 2q12 that harbors a polymorphism (rs917997) associated with several autoimmune diseases, including celiac disease (CeD) (13), inflammatory bowel disease (14), and T1D (15). The expression level of this lncRNA is significantly decreased in small intestinal biopsy samples from patients with CeD, and a recent study described that regulates the expression of a subset of CeD-associated inflammatory genes through interaction with heterogeneous nuclear ribonucleoprotein D 7-Dehydrocholesterol (16). Interestingly, while the risk signal in CeD corresponds to the rs917997*T allele, the opposite allele (rs917997*C) is the risk allele in T1D, suggesting that the single nucleotide polymorphism (SNP) may alter the 7-Dehydrocholesterol function of this lncRNA in a tissue- or disease-specific mode. In the current study, we describe a molecular mechanism by which T1D-associated regulates virus-induced pancreatic -cell inflammation. We observed that acts as a linker between the RNA binding protein PCBP2 and the 3UTR of to stabilize the mRNA of participates in pancreatic -cell inflammation via regulation of the STAT1 signaling pathway. This pathway plays a crucial role in T1D-related -cell dysfunction and death, therefore, the ability of to influence STAT1 activation supports its role in the pathogenesis of the disease. These results serve as a proof of concept of the role of T1D-associated lncRNAs in the progressive loss of pancreatic -cells in T1D and open an avenue for the development of therapeutic approaches based 7-Dehydrocholesterol on lncRNA expression modification. Results Is Expressed in Human Pancreatic -Cells, Is Up-Regulated by Viral Infections, and Correlates with Expression in Human Pancreatic Islets. We first evaluated the expression of in the human pancreatic -cell line EndoC-H1 compared with a set of human tissues. As.