Alterações na mucosa intestinal de camundongos NOD precedem o desenvolvimento da diabetes tipo 1

• Ano de defesa: 2019
• Autor(a) principal: Mariana Camil Goncalves Miranda Waldetario
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; Programa de Pós-Graduação em Bioquímica e Imunologia; UFMG
• Palavras-chave em Português: mucosa intestinal; Diabetes tipo 1; IgA secretora; ILCs; tolerância oral; Bioquímica e Imunologia; Diabetes Mellitus Tipo 1; Mucosa Intestinal; Imunoglobulina A Secretora
• Link de acesso: http://hdl.handle.net/1843/64210

Alterations in the composition of the intestinal microbiota have been associated with development of type 1 diabetes (DM1), but little is known about changes in intestinal homeostasis that contribute to development and disease pathogenesis. In this stood 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 nonobese 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 bacteriabound secretory IgA, as well as an altered IEL profile. These disturbances correlated with bacteria translocation to the pancreatic lymph node possibly contributing to DM1 onset. The composition of the fecal microbiota was altered in yang 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 decreased of Th2 cells, ILC2 and Treg cells in the small intestine. Importantly, most of these gut alterations precede the onset of insulitis suggesting that these changes may be involved in the early events that trigger the disease. Disorders in the intestinal mucosa of NOD mice can potentially interfere with the development of DM1 due the close relationship between the gut and the pancreas. Understanding these early alterations is important for the design of novel therapeutic strategies for DM1 prevention.