Study of the Foxn1 involvement in thymic atrophy of diabetic mice

• Grant number: 13/05055-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 09, 2013
• End date: March 08, 2014
• Field of knowledge: Biological Sciences - Immunology - Immunogenetics
• Principal Investigator: Liana Maria Cardoso Verinaud
• Grantee: Carolina Francelin de Andrade
• Supervisor: Catherine Clare Blackburn
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University of Edinburgh, Scotland
• Associated to the scholarship: 10/19558-3 - Studies in leptin effects in thymus atrophy and immune responses during experimental diabetes, BP.DR

Abstract

Thymus is the primary lymphoid organ responsible for T lymphocytes development. Thymocyte intrathymic migration is essential for its maturation, process through which they receive the necessary signal for their survival, proliferation and differentiation. These signals are derived from thymic stromal components comprising the thymic epithelial cells, fibroblasts, extracellular matrix components as well as hematopoietic cells (macrophages and dendritic cells).Also, thymic epithelial cells form the framework for the migration of thymocytes. The formation and maintenance of the thymic epithelium are under Foxn1 strict control. This transcription factor has the ability to control the expression of many genes that determine the differentiation of thymic epithelial cells precursor and the expression of genes that encode to proteins that form the biochemical cascades required for maintaining such living cells, and therefore remains unchanged thymic epithelium. In our laboratory, we have worked with the model of thymic atrophy in diabetes induced by alloxan. Through this model, we found that atrophy before diabetes is concomitant to the serum leptin levels decrease and this metabolic change is strongly related to the cellular changes observed in the thymic epithelium of diabetic animals. Today we know that the atrophic thymus of diabetic animals show changes in the arrangement of epithelial cells in addition to reduced cellularity and total cortical and medullary epithelium. Knowing that the thymus and the immune system as a whole is under-rigid neuroendocrine control and the secretion of hormones that make up the hypothalamic-pituitary gland has a direct consequence on the lymphoid organs; intend, through the development of this work, evaluate the role of the transcription factor Foxn1 and analyzing the involvement of leptin in the regulation of this transcription factor in thymus of diabetic animals. This project also aims to generate data that can corroborate the better understanding of the issues that were previously raised on a regular doctoral project (FAPESP-2010/19558-3), to which this project is linked. (AU)