Stability and plasticity of Th9 cells: role of PU.1

• Grant number: 13/27028-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: April 01, 2014
• End date: March 31, 2015
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandra Ivo de Medeiros
• Grantee: Felipe Fortino Verdan da Silva
• Supervisor: Mark H. Kaplan
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: Indiana University-Purdue University Indianapolis, United States
• Associated to the scholarship: 11/20199-0 - PGE2 immunomodulatory role in Th17 differentiation during the phagocytosis of infected apoptotic cells event, BP.DR

Abstract

The newest Th cell subset to be proposed is the IL-9 secreting Th9 subset. IL-9 has long been implicated as a contributor to the inflammation observed during an allergic response. To further support this finding Dr. Kaplan's lab has demonstrated that blocking IL-9 activity as allergic inflammation develops decreases pulmonary infiltration. The recent emergence of Th9 cells as a major source of IL-9 has led to an abundance of questions and investigations that are aimed at affirming these cells as distinct from all other Th subsets. The differentiation of this new Th cell depends on the presence of the transcription factor PU.1. Moreover, Dr. Kaplan's group found diminished allergic inflammation in mice that have T cell-specific deletion of PU.1, which suggest PU.1 is an important regulator of allergic inflammation. There is a lack of fundamental understanding surrounding the phenotype of Th9 and the role of these cells in the progression of allergic inflammation beyond their secretion of IL-9, IL-10 and chemokines. Similarly to other Th cell subsets, one of the first steps to better understanding the Th9 phenotype will involve characterization of the transcription factor network that regulates the Th9 phenotype. In this application, we propose to determine the stability and plasticity of the Th9 phenotype in vitro in the presence and absence of PU.1. Also, the maintenance of Th9 phenotypes will be tested in vivo using two models of allergic inflammation with the help of reporter mice. (AU)