Evaluation of the immune-endocrine-microbiota axis in intestinal inflammation in mice with acute graft-versus-host disease

• Grant number: 23/15783-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2024
• End date: September 30, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Gislane Lelis Vilela de Oliveira
• Grantee: Jefferson Luiz da Silva
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Allogeneic bone marrow transplantation (allo-BMT) has been used as a therapeutic procedure for hematological malignancies and diseases unresponsive to chemotherapy. Despite its increasing application, allo-BMT is associated with significant morbidity and mortality. Graft-versus-host disease (GvHD) is the main complication and cause of death after BMT, affecting 30-70% of patients. Studies have shown the relationship between the immunoendocrine-microbiota axis in inflammatory bowel diseases and its association with clinical outcomes. The objective of this work will be to evaluate changes in the immunoendocrine-microbiota axis during intestinal inflammation in mice subjected to allo-BMT and correlate with the clinical score of acute GvHD. This study will be submitted to the Ethics Committee on the use of Animals. Allo-BMT will be standardized from C57BL/6 CD45.1 to Balb/c, without and with adrenalectomy. Balb/c animals will be irradiated at 900 cGy conditioning, and after 3 hours, they will receive 5x106 bone marrow cells and 2x106 C57Bl/6 splenic T cells. We will monitor weight and clinical score daily. Sample collection will occur 20 days post-BMT. We will evaluate the cellular immunophenotypic profile of lymphoid organs and tissue inflammatory pattern, as well as circulating cytokines and cortisol and extra-adrenal production. We will also analyze the intestinal microbiota, markers of bacterial permeability and translocation and tissue gene expression. We expect to find significant changes in the immunoendocrine-microbiota axis during intestinal inflammation in mice subjected to allo-BMT, which develop GvHDa, and to understand how these axis work together and influence the post-transplant clinical response.