Role of the canonical and non-canonical NF-kB pathway in transcriptional control of T regulatory cells induction

• Grant number: 10/13234-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2010
• End date: February 29, 2012
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marco Antonio Zago
• Grantee: Felipe Saldanha de Araujo
• Host Institution: Hemocentro de Ribeirão Preto. Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Secretaria da Saúde (São Paulo - Estado). Ribeirão Preto , SP, Brazil

Abstract

CD4+CD25+ regulatory lymphocytes (Treg) are recognized as the most important regulatory cells of the immune system and are involved in immune tolerance, autoimmunity, inflammation, transplantation, cancer and HIV infection. Tregs can be naturally occurring (nTregs), derived from the thymus or induced in the periphery from naive cells (iTregs). Both lymphocytes (nTregs and iTregs) have similar phenotype and expression of the transcription factor forkhead box P3 (Foxp3) by Treg appears to be essential for the maintenance of immune homeostasis. Mutations involving the transcription factor results in a syndrome characterized by multiple autoimmune diseases, leading the patient to death in infancy. Moreover, the deficiency in number or function of Tregs is directly associated with the development of various autoimmune diseases. Recent studies point to an important role NF-kB pathway in the transcription of Foxp3 in Tregs originated in the thymus. While recognizing the importance of tumor growth factor beta (TGF-²) and the TCR signaling pathway in the generation of iTregs, the molecular mechanisms that lead to the induction of these cells are largely unknown. The aims of this study is to evaluate and compare the involvement of different transcription factors (Real, RelB and c-Rel) involved in signaling via NF-kB in three cell populations, cells naive, effector lymphocytes CD4 + T lymphocytes iTregs generated from naive lymphocytes obtained from cord blood, by chromatin immunoprecipitation methodology with microarrays of promoter regions of the human genome. (AU)