Role of Blimp-1 in differentiation and function of Th9 cells

• Grant number: 12/08240-8
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): October 01, 2012
• Effective date (End): September 30, 2016
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: João Santana da Silva
• Grantee: Luciana Benevides
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto, SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

T lymphocytes are essential for the development of immune responses consist of different sub-populations with specific functions. Currently, varieties of subtypes of CD4+ T cells have been identified, as well as transcription factors which regulate differentiation and effector function of these cells. Among these subtypes have been described CD4+ T cells producing IL-9 (Th9), but the factors involved in the regulation of these cells have not yet been elucidated. Transcription factors and cytokines represent two classes of signals essential for the process of cell differentiation. The binding of cytokines on their respective receptors results in activation of protein (STATs) and other transcription factors that induce or repress transcription of specific genes in each cell line, allowing the survival, proliferation and differentiation of these cells. Among the transcription factors, Blimp-1 (protein induced in mature B lymphocytes) has been associated with terminal differentiation of effector T cells. In this context, we hypothesized that Blimp-1 negatively regulates the differentiation process of Th9 cells. Thus, we believe that TGF-² can inhibit the expression of Blimp-1, even in combination with IL-4, leading to differentiation Th9 cell. In addition, the absence of Blimp-1 promotes the expression of essential regulatory as PU.1 and IRF-4 aiding in maintenance of phenotype Th9 cell. Therefore, this study aims to evaluate the role of Blimp-1 during the differentiation and function of Th9 cells in vitro and in vivo. For this, cells obtained from mice deficient in conditionally Blimp-1, in which only CD4+ cells are deficient in Blimp-1 are used in this study. First evaluate whether Blimp-1 is important for differentiation and function of in vitro Th9 cells. Additionally, we will evaluate the role of Blimp-1 in development Th9 cell in vivo. To achieve this objective, two models of inflammation: intestinal (induced by T. gondii) and of the airways (asthma). Finally, as investigate Blimp-1 is capable of regulating the production of IL-9. Understanding the transcriptional mechanisms responsible for the differentiation and effector function of Th9 cells and IL-9 may open perspectives for the development of new therapeutic approaches in various inflammatory diseases.