Project Details
Projekt
The role of Interferon Regulatory Factor 4 in the regulation of T-cell memory
Subject Area
Immunology
Term
from 2017 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 389124112
The transcription factor Interferon Regulatory Factor 4 (IRF4) is essential for the differentiation of peripheral CD8+ T cells to effector T cells and of CD4+ T cells to different TH-cell subsets. There is further evidence that magnitude and kinetics of IRF4 expression determine the fate of T-cell maturation. The main aim of our current study is a better understanding of the mechanisms controlling memory T-cell formation, persistence and function. The underlying hypothesis of the project is that IRF4 is required for the stability of memory T cells and for the maintenance of the differentiation status of TH-cell subsets. To test this hypothesis, we plan to apply in vitro studies and mouse infection models. In the Listeria monocytogenes infection model, we will investigate IRF4 expression levels in different CD4+ and CD8+ memory T-cell populations, e.g. effector memory, central memory and tissue resident memory T cells. T cells from mice with inducible Irf4 deletion or with forced Irf4 expression will be analysed in this infection model to determine the impact of IRF4 on the persistence and function of CD4+ and CD8+ memory cell subsets and on the stability of the CD4+ TH1-cell differentiation status. Using CD4+ T cells with inducible Irf4 deletion in mouse infection models for Strongyloides ratti and for Citrobacter rodentium, we will further examine the IRF4 requirement for the stability of TH2 and TH17 cells, respectively. Finally, in vitro-generated Irf4-deficient memory T cells will be utilized to characterize the function of IRF4 on fundamental cellular mechanisms, such as the response to survival cytokines or energy metabolism in memory T cells. We expect that our results will reveal the function of IRF4 in memory T-cell formation and maintenance, and in stability of TH-cell lineages. Although our study mainly aims at clarifying fundamental mechanisms of T-cell regulation, results might identify regulatory pathways that can be targeted to modulate T-cell responses in infection, chronic inflammation or autoimmunity.
DFG Programme
Research Grants
