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Evaluation of notch receptors and ligands in thymocytes, natural T regulatory cells and dendritic cells in the human thymus

Grant number: 12/01248-3
Support Opportunities:Regular Research Grants
Duration: July 01, 2012 - June 30, 2014
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Alberto José da Silva Duarte
Grantee:Alberto José da Silva Duarte
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Jefferson Russo Victor ; Luciana Bento de Souza


The thymus is an organ responsible to T lymphocytes maturation, and during this process lymphocytes give rise in different developmental phases of maturation which can be phenotypically identified such as CD4-CD8-, CD4+CD8+, CD4+CD8- and CD4-CD8+. The result of thymic maturation is the generation of CD4 and CD8 mature T lymphocytes (95% of emigrant lymphocytes) and other specialized subpopulations.The process of thymic maturation involves different signaling pathways, and in the last years the Notch signaling is believed to be involved in this process. Notch signaling pathway is composed by a family of receptors and ligands that has shown involvement in several cell lineages development.Among special subset of cells matured in the thymus, stand out T CD4 lymphocytes with regulatory potential upon immune system, called by natural T regulatory cells (nTreg). This subset of cells is generated specifically in thymic medulla where grouped epithelial cells and thymic dendritic cells (tDCs) are located in the Hassal's Corpuscles. For not being clearly described, the Notch signaling could be involved in the generation of nTreg. Few studies in the literature that suggests the participation of Notch receptors and ligands in the generation of T CD4, T CD8 lymphocytes and nTreg has been developed in murine models. Thus, our work aims to evaluate the expression and occurrence of genes and molecules of Notch receptors and ligands in different developmental thymocytes subpopulations, nTreg, thymic stromal cells and tDCs in human thymus. Successfully, this study will collaborate with the knowledge of immune system development, tolerance and autoimmunity, yielding future therapies development to manipulate the immune system. (AU)

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