Innate immunity and intestinal microbiota in the development of Type 1 diabetes

Li Wen, et al. Nature 455 1109-1113 (2008)

Speacker : Kuan-Ru Chen                           Time:14:00~15:00

Commentator: Dr. Chi-Chang Shish                   Place: Room 601

Abstract:

Insulin is a hormone that is needed to convert sugar into energy. Diabetes is a disease when body does not produce or properly use insulin, and individuals typically develop acute complications and long-term complications. Type 1 diabetes (T1D) is a T cell-mediated autoimmune process that destroys the insulin producing βcells of the pancreas and there is no longer sufficient insulin production to regulate blood glucose levels. T1D is influenced by genetic and environmental factors. Gut immunity, intestinal flora and Toll-like receptor were reported to have co-relations with TID. The incidence of spontaneous T1D can be affect by microbial environment or various microbial products, but the mechanism by which innate immunity leads to diabetes prevention is not fully understood. First, the authors find that specific pathogen free (SPF) MyD88^KO NOD mice do not develop T1D, and think MyD88 signaling was required for T1D. Second, they find that T cells of MyD88^KO NOD mouse have no tolerance but decrease in pancreatic lymph nodes. Third, the germ-free MyD88^KO NOD mice develop robust diabetes, but when colonization of these germ-free MyD88^KO NOD mice with an altered Schaedler flora (ASF) attenuates T1D. They think that commensal microbes can attenuate T1D and activation of anti-islet T cell is MyD88-independ. Finally, the caecal microbiota of MyD88^KO NOD mouse is different from MyD88^KO/+ NOD and that exposure to the microbiota of specific pathogen-free MyD88^KO NOD donors attenuates T1D in germ-free NOD newborn progeny. The authors find MyD88^KO NOD can change intestinal microbiota and then attenuate T1D. These findings indicate the interaction of innate immunity and intestinalmicrobiota could affect the development of T1D, and provide new therapeutic options for T1D in the future.

References：

1. F. Calcinaro , et al.2005.Oral probiotic administration induces interleukin-10 production and prevents spontaneous autoimmune diabetes in the non-obese diabetic mouse. Diabetologia, 48: 1565–1575

2. Marie-Claude Gagnerault, et al. 2002.Pancreatic Lymph Nodes Are Required for Priming of Cell Reactive T Cells in NOD Mice. J. Exp. Med 189: 331–339