Evaluation of the expression profile and function of AIM2 inflammasome in intestinal mucosa during diabetes type 1 experimental

• Grant number: 16/25116-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2017
• End date: June 30, 2018
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Daniela Carlos Sartori
• Grantee: Jefferson Antonio Leite
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 12/10395-0 - Role of NLRs receptors in immunoregulation mechanisms of the type 1 and 2 diabetes: identification of potential therapeutic targets, AP.JP

Abstract

Alarming rates of Diabetes Melito (DM) prove that this disease has become a major problem in the area of public health worldwide. Type 1 diabetes (DM1) is an autoimmune disease determined by genetic factors and the interference of environmental factors. This disease is characterized by dysfunction of the endocrine pancreas resulting from the selective destruction of ² cells present in the pancreatic and insulin-producing islets by autoreactive T lymphocytes, leading the individual to a state of hyperglycemia.Studies developed by our research group found that alteration of the intestinal microbiota, associated with translocation of bacteria to the pancreatic lymph nodes, leads to activation of the NOD2 receptor in myeloid cells and expression of cytokines leading to the process of insulitis and subsequent DM1. In this context, some proinflammatory cytokines, such as IL-1², IL-18 and IL-33, become biologically active after proteolytic cleavage by caspase-1 arising from the formation of the inflammasome, consisting of a molecular platform, Of the Nod-like receptors (NLRs) and Aim-like receptors (ALRs), which include NLRP1, NLRP3, NLRP6, NLRC4 and AIM2, respectively. A recent study has shown that the AIM2 receptor contributes to the maintenance of the intestinal barrier and protects against the development of colitis. Thus, our hypothesis is that activation of the AIM2 receptor is important in intestinal mucosal immunity and control of bacterial translocation, thus causing resistance to experimental DM1.Therefore, we will study the activation pathways and the functional role of the AIM2 inflammome in the development of streptozotocin-induced (STZ) DM1. In addition, we intend to investigate the involvement of this receptor in the modulation of the cellular immune response during the progression of DM1. The execution of this project will be of great relevance, since the identification of molecular targets associated with the immunoregulation of DM1 may contribute to the implementation of new immunotherapies that may be used in the future in the treatment of diabetic patients. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LEITE, JEFFERSON ANTONIO; PESSENDA, GABRIELA; GUERRA-GOMES, ISABEL C.; MENDONCA DE SANTANA, ALYNNE KAREN; PEREIRA, CAMILA ANDRE; CAMPOS COSTA, FREDERICO RIBEIRO; RAMOS, SIMONE G.; ZAMBONI, DARIO SIMOES; CAETANO FARIA, ANA MARIA; DE ALMEIDA, DANILO CANDIDO; et al. The DNA Sensor AIM2 Protects against Streptozotocin-Induced Type 1 Diabetes by Regulating Intestinal Homeostasis via the IL-18 Pathway. CELLS, v. 9, n. 4, APR 2020. (12/10395-0, 16/25116-0, 13/08216-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

LEITE, Jefferson Antonio. The activation of AIM2 receptor in the intestinal mucosal protects against experimental type 1 diabetes. 2018. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.