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

@article{Wen_et_al08, abstract = {Type 1 diabetes (T1D) is a debilitating autoimmune disease that results from T-cell-mediated destruction of insulin-producing beta-cells. Its incidence has increased during the past several decades in developed countries, suggesting that changes in the environment (including the human microbial environment) may influence disease pathogenesis. The incidence of spontaneous T1D in non-obese diabetic (NOD) mice can be affected by the microbial environment in the animal housing facility or by exposure to microbial stimuli, such as injection with mycobacteria or various microbial products. Here we show that specific pathogen-free NOD mice lacking MyD88 protein (an adaptor for multiple innate immune receptors that recognize microbial stimuli) do not develop T1D. The effect is dependent on commensal microbes because germ-free MyD88-negative NOD mice develop robust diabetes, whereas colonization of these germ-free MyD88-negative NOD mice with a defined microbial consortium (representing bacterial phyla normally present in human gut) attenuates T1D. We also find that MyD88 deficiency changes the composition of the distal gut microbiota, and that exposure to the microbiota of specific pathogen-free MyD88-negative NOD donors attenuates T1D in germ-free NOD recipients. Together, these findings indicate that interaction of the intestinal microbes with the innate immune system is a critical epigenetic factor modifying T1D predisposition.}, author = {Wen, Li and Ley, Ruth E. and Pavel and Stranges, Peter B. and Avanesyan, Lia and Stonebraker, Austin C. and Hu, Changyun and Wong, Susan F. and Szot, Gregory L. and Bluestone, Jeffrey A. and Gordon, Jeffrey I. and Chervonsky, Alexander V.}, citeulike-article-id = {3314338}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature07336}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature07336}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18806780}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18806780}, day = {21}, doi = {10.1038/nature07336}, issn = {0028-0836}, journal = {Nature}, keywords = {gut, immunity, t1d}, month = {September}, posted-at = {2008-10-21 14:11:13}, priority = {2}, publisher = {Nature Publishing Group}, title = {Innate immunity and intestinal microbiota in the development of Type 1 diabetes}, url = {http://dx.doi.org/10.1038/nature07336}, year = {2008} }

TY - JOUR ID - Wen_et_al08 L3 - citeulike-article-id:3314338 N2 - Type 1 diabetes (T1D) is a debilitating autoimmune disease that results from T-cell-mediated destruction of insulin-producing beta-cells. Its incidence has increased during the past several decades in developed countries, suggesting that changes in the environment (including the human microbial environment) may influence disease pathogenesis. The incidence of spontaneous T1D in non-obese diabetic (NOD) mice can be affected by the microbial environment in the animal housing facility or by exposure to microbial stimuli, such as injection with mycobacteria or various microbial products. Here we show that specific pathogen-free NOD mice lacking MyD88 protein (an adaptor for multiple innate immune receptors that recognize microbial stimuli) do not develop T1D. The effect is dependent on commensal microbes because germ-free MyD88-negative NOD mice develop robust diabetes, whereas colonization of these germ-free MyD88-negative NOD mice with a defined microbial consortium (representing bacterial phyla normally present in human gut) attenuates T1D. We also find that MyD88 deficiency changes the composition of the distal gut microbiota, and that exposure to the microbiota of specific pathogen-free MyD88-negative NOD donors attenuates T1D in germ-free NOD recipients. Together, these findings indicate that interaction of the intestinal microbes with the innate immune system is a critical epigenetic factor modifying T1D predisposition. JF - Nature SN - 0028-0836 TI - Innate immunity and intestinal microbiota in the development of Type 1 diabetes PB - Nature Publishing Group KW - gut KW - immunity KW - t1d AU - Wen, Li AU - Ley, Ruth AU - Pavel AU - Stranges, Peter AU - Avanesyan, Lia AU - Stonebraker, Austin AU - Hu, Changyun AU - Wong, Susan AU - Szot, Gregory AU - Bluestone, Jeffrey AU - Gordon, Jeffrey AU - Chervonsky, Alexander PY - 2008/09/21/ UR - http://dx.doi.org/10.1038/nature07336 ER -