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Clin Immunol. 2009 Jul;132(1):103-15. doi: 10.1016/j.clim.2009.02.007. Epub 2009 Mar 26.

DNA microarray analysis for the identification of innate immune pathways implicated in virus-induced autoimmune diabetes.

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  • 1Department of Pediatrics, Barbara Davis Center for Childhood Diabetes, University of Colorado Health Science Center, 1775 Aurora Ct., Mail Stop B-140, Aurora, CO 80045, USA.


We have recently demonstrated that upregulation of the innate immune system plays a key role in KRV-induced autoimmune diabetes in the BBDR rat, but the nature of this proinflammatory reaction has not yet been addressed. Using a DNA microarray approach, we identified 569 genes upregulated in pancreatic lymph nodes following virus infection. Among the most highly activated are IL-1 pathways, IFN-gamma-induced chemokines, and genes associated with interferon production and signaling. Ex vivo and in vitro studies indicate that KRV upregulates proinflammatory cytokines and chemokines in B lymphocytes and Flt-3L-induced plasmacytoid DCs (pDCs). Finally, in contrast to KRV, infection of BBDR rats with the non-diabetogenic KRV homologue H-1 parvovirus fails to induce a robust proinflammatory response in pancreatic lymph nodes. Our findings provide new insights into KRV-induced innate immune pathways that may play a role in early mechanisms leading to islet inflammation and diabetes.

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