Uncovering molecular mechanisms involved in STING-mediated regulation of Th17 cell pathogenicity

• Grant number: 21/08800-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: December 01, 2021
• End date: November 30, 2022
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: José Carlos Farias Alves Filho
• Grantee: Luis Eduardo Alves Damasceno
• Supervisor: Tim D. Sparwasser
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Johannes Gutenberg University Mainz (JGU), Germany
• Associated to the scholarship: 18/17542-4 - The role of the STING signaling pathway in the regulation of Th17 cell pathogenicity and its implication for autoimmunity, BP.DR

Abstract

Th17 cells comprise a subpopulation of CD4 T cells widely described to mediate inflammation in autoimmune diseases. Over the last few years, a range of studies evidenced external and intrinsic factors regulating the transcriptional profile of Th17 cells, thereby affecting their pathogenic potential and revealing their context-dependent plasticity. The adaptor protein STING has been reported as an important component of the intracellular machinery governing DNA sensing, being poorly explored in T cells. In this sense, our data demonstrate that STING activation in Th17 cells, in vitro, promotes a reduced ability of these cells to produce IL-17A and increased expression of the anti-inflammatory cytokine IL-10, suggesting that STING reprogram Th17 cells towards a profile with reduced pathogenic potential. However, the mechanisms by which STING regulates the pathogenicity of these cells are still unknown. Therefore, the main aim of this project is to gain a better understanding of the molecular mechanisms involved in the STING-driven regulatory network in Th17 cells. In order to reach this goal, we have set up a collaborative study with Prof. Tim Sparwasser from Johannes Gutenberg-University Mainz, in Germany, who is expert in the field of T cell biology with publications in high-impact journals. To this end, we are applying for the BEPE internship program to spend 12 months in his laboratory to develop this project. (AU)