Project description
Cytosolic DNA sensing drives CD4 T-cell differentiation
Cellular defence against pathogens involves the detection of pathogen-associated molecular patterns, including deoxyribonucleic acid (DNA), which is recognised by host myeloid cells through toll-like receptor 9 (TLR9) binding. Recent studies suggest that innate immune cells also recognise cytoplasmic DNA via cytosolic DNA sensors and TLR9-independent signalling. Importantly, the contribution of cytosolic DNA sensors to the differentiation of CD4 T-cells, which is essential for driving adaptive immune responses, has not been investigated. The ERC-funded CD4DNASP project will investigate the role of cytosolic DNA sensing pathways in CD4 T-cell differentiation. The objective is to identify the molecular mechanisms of transcriptional events that result in T-cell differentiation triggered by DNA sensing.
Objective
This proposal aims to investigate the role of cytosolic DNA sensing pathways in CD4 T cell differentiation.
Cellular host defense to pathogens relies on the detection of pathogen-associated molecular patterns including deoxyribonucleic acid (DNA), which can be recognized by host myeloid cells through Toll-like receptor (TLR) 9 binding. Recent evidence however suggests that innate immune cells can also perceive cytoplasmic DNA from infectious or autologous origin through cytosolic DNA sensors triggering TLR9-independent signaling. Activation of cytosolic DNA sensor-dependent signaling pathways has been clearly shown to trigger innate immune responses to microbial and host DNA, but the contribution of cytosolic DNA sensors to the differentiation of CD4 T cells, an essential event for shaping adaptive immune responses, has not been documented. This proposal aims to fill this current knowledge gap.
We aim to decipher the molecular series of transcriptional events triggered by DNA in CD4 T cells that ultimately result in altered T cell differentiation. This aim will be addressed by combining in vitro and in vivo approaches such as advanced gene expression analysis of CD4 T cells and use of transgenic and gene-deficient mice. Structure activity relationship and biophysical studies will also be performed to unravel novel immunomodulators able to affect CD4 T cell differentiation.
Fields of science
Keywords
Programme(s)
Topic(s)
Funding Scheme
ERC-STG - Starting GrantHost institution
75654 Paris
France