OPPOSING EFFECTS OF THE GUT MICROBIOME ON AUTOIMMUNE TYPE 1 DIABETES AND INFLAMMATORY BOWEL DISEASE IN IL10-DEFICIENT MICE
Alexandria Bobe1, Patrick Moore2, Susan Devkota3, Vanessa Leone1, Betty Theriault1, Mark Musch1, Alexander Chervonsky1, Mark Atkinson4, Christopher Rhodes1, Eugene Chang1.
1The University of Chicago, Chicago, IL, 2Kovler Diabetes Center, The University of Chicago, Chicago, IL, 3Joslin Diabetes Center, Harvard Medical School, Boston, MA, 4Diabetes Institute, University of Florida, Gainesville, FL.
The incidence of autoimmune Type 1 diabetes (T1D) and inflammatory bowel disease (IBD) is rising across all ethnic groups, primarily associated with cultural westernization. The human gut microbial organ has been highlighted as a major player in IBD pathophysiology; however, far less is known about the role of the gut microbiome in T1D onset and progression. In the IBD-prone C57Bl/6 interleukin-10 deficient (IL10KO) mouse model, the lack of gut microbiota under germ-free (GF) conditions prevents IBD development. We present here our findings that C57Bl/6 GF IL10KO mice develop pancreatic lymphocytic infiltration that resembles T1D insulitis instead of IBD independent of the major MHC risk haplotypes found in other T1D susceptibility models. We hypothesize IL10 and gut microbiota may be protective for beta cells. Preliminary studies are under way to determine whether GF IL10KO mice exhibit increased risk for insulitis associated with T1D and to identify key immune mediators. Histological analyses of pancreata reveal approximately 41% of GF IL10KO mice develop islet inflammation. Immunofluorescent staining confirms islet infiltrates are positive for immunological markers indicative of T1D insulitis: major histocompatibility class I (MHC-I); dendritic CD11c; pan-macrophage CD68; and CD3, CD4, and CD45R lymphocytes. We believe the GF IL10KO mouse represents a novel model for autoimmune T1D that will allow us to investigate the early stages of autoimmune development and increase our understanding of the etiological mechanisms of autoimmune disease.