The impact of microbial products on the modulation of CD8+IL-9+ t cells in experimental lung inflammation

• Grant number: 16/03532-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2016
• Effective date (End): June 30, 2018
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Rafael Ribeiro Almeida
• Grantee: Raquel de Souza Vieira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Naive CD4+ and CD8+ T cells develop into Th9 and Tc9 cells in the presence of IL-4 and TGF-b. Tc9 cells support Th2-mediated experimental lung inflammation by increasing the symptoms. Recently, it was demonstrated that animals fed with a rich-fiber diet were protected from experimental lung inflammation due to the modulation of short chain fatty acid (SCFA)-producing microbiota. Additionally, it has been found that the SCFA butyrate reduce the expression of the transcription factor PU.1 in dendritic cells, which in Th9 cells is essential for IL-9 production. Furthermore, butyrate treatment was responsible for enhancing FOXP3 expression in CD4+ T cells, a transcription factor known for being an inhibitor of IL-9 in Tc9 cells. Therefore, we hypothesize that butyrate protects against experimental lung inflammation by blocking the development of Tc9 cells. This blockage will be given either by PU.1 inhibition or FOXP3 induction in CD8+ T cells. In this project, we aim to study the impact of butyrate on the in vitro development of Tc9 cells by evaluating its influence on the expression of IL-9-related transcription factors and FOXP3. We also intend to determine whether butyrate-mediated FOXP3 induction in naïve CD8+ T cells will result in regulatory T cells. Finally, we wish to evaluate the therapeutic potential of butyrate in the context of experimental lung inflammation.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VIEIRA, RAQUEL DE SOUZA; CASTOLDI, ANGELA; BASSO, PAULO JOSE; HIYANE, MEIRE IOSHIE; SARAIVA CAMARA, NIELS OLSEN; ALMEIDA, RAFAEL RIBEIRO. Butyrate Attenuates Lung Inflammation by Negatively Modulating Th9 Cells. FRONTIERS IN IMMUNOLOGY, v. 10, JAN 29 2019. (16/03532-1, 15/26682-6, 15/13817-0)