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- Title
Frontline Science: Abnormalities in the gut mucosa of non‐obese diabetic mice precede the onset of type 1 diabetes.
- Authors
Miranda, Mariana Camila Gonçalves; Oliveira, Rafael Pires; Torres, Lícia; Aguiar, Sarah Leão Fiorini; Pinheiro‐Rosa, Natalia; Lemos, Luísa; Guimarães, Mauro Andrade; Reis, Daniela; Silveira, Tatiany; Ferreira, Ênio; Moreira, Thaís Garcias; Cara, Denise Carmona; Maioli, Tatiani Uceli; Kelsall, Brian L.; Carlos, Daniela; Faria, Ana Maria Caetano
- Abstract
Alterations in the composition of the intestinal microbiota have been associated with development of type 1 diabetes (T1D), but little is known about changes in intestinal homeostasis that contribute to disease pathogenesis. Here, we analyzed oral tolerance induction, components of the intestinal barrier, fecal microbiota, and immune cell phenotypes in non‐obese diabetic (NOD) mice during disease progression compared to non‐obese diabetes resistant (NOR) mice. NOD mice failed to develop oral tolerance and had defective protective/regulatory mechanisms in the intestinal mucosa, including decreased numbers of goblet cells, diminished mucus production, and lower levels of total and bacteria‐bound secretory IgA, as well as an altered IEL profile. These disturbances correlated with bacteria translocation to the pancreatic lymph node possibly contributing to T1D onset. The composition of the fecal microbiota was altered in pre‐diabetic NOD mice, and cross‐fostering of NOD mice by NOR mothers corrected their defect in mucus production, indicating a role for NOD microbiota in gut barrier dysfunction. NOD mice had a reduction of CD103+ dendritic cells (DCs) in the MLNs, together with an increase of effector Th17 cells and ILC3, as well as a decrease of Th2 cells, ILC2, and Treg cells in the small intestine. Importantly, most of these gut alterations precede the onset of insulitis. Disorders in the intestinal mucosa of NOD mice can potentially interfere with the development of T1D due the close relationship between the gut and the pancreas. Understanding these early alterations is important for the design of novel therapeutic strategies for T1D prevention.
- Subjects
TYPE 1 diabetes; INSULIN resistance; TH2 cells; MUCOUS membranes; INTESTINAL mucosa; INTESTINAL tumors; HYPOKINESIA
- Publication
Journal of Leukocyte Biology, 2019, Vol 106, Issue 3, p513
- ISSN
0741-5400
- Publication type
Article
- DOI
10.1002/JLB.3HI0119-024RR