Effect of the administration of Lactococcus lactis expressing HSP65 on the induction of tolerance mediated by regulatory T cells and on the immunoregulation of DM1 in an experimental model.

• Grant number: 22/02762-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): November 01, 2022
• Effective date (End): February 29, 2024
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Daniela Carlos Sartori
• Grantee: Jefferson Elias Oliveira
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 18/14815-0 - Evaluation of the intestinal microbioma profile and of the therapeutic potential of intervention strategies in the immunopathogeny of type 1 and 2 Diabetes, AP.JP2

Abstract

Diabetes mellitus is a group of metabolic diseases characterized mainly by chronic hyperglycemia, resulting from the absence or defect in the functionality of insulin. The immunopathology of type 1 diabetes mellitus (DM1) results from the presence of autoantibodies and lymphocytes that react against ²-cell antigens present in the pancreatic islets, leading to insulin deficiency. Its etiology is determined by genetic and environmental factors, such as infections, diet and intestinal microbiota. Probiotics have been extensively studied as forms of therapy in various diseases, and basically exert their beneficial effects through different pathways, which include competitive exclusion, antibacterial effects, modulation of the immune response and maintenance of the integrity of the intestinal barrier. Interestingly, a reduction in autoantibodies was observed in children who received probiotics. Lactococcus lactis is a gram-positive probiotic bacterium that has been used in the production of heterologous proteins of therapeutic interest. Its use is quite safe, and its ability to secrete soluble molecules and deliver cytokines and self antigens has already been demonstrated. Hsp65 proteins are important therapeutic targets, as they are highly conserved and homologous proteins in many species and can induce oral tolerance in autoimmune diseases. In this sense, the objective of this work is to evaluate the effect of L. lactis expressing Hsp65 on the immunopathogenesis of DM1. Additionally, we intend to identify the possible immunological mechanisms of regulation in the intestinal mucosa and in the pancreatic tissue. This study will allow progress in the development of new therapeutic forms that may prevent the onset or minimize the progression of DM1.