Project description:Stimulus-specific gene expression programs are enabled by enhancers, on which stimulus-regulated transcription factors (SRTFs) can land in a cell type- and stimulus-dependent manner. In this study, we identified the key features of enhancers that mediate differential responses to Toll-like receptor (TLR)-stimulation. We characterized the TLR3- and TLR9-induced programs and enhancers in CD8+ dendritic cells.The relevance of these features has been confirmed via machine learning application and by mapping SRTF-binding.
Project description:Stimulus-specific gene expression programs are enabled by enhancers, on which stimulus-regulated transcription factors (SRTFs) can land in a cell type- and stimulus-dependent manner. In this study, we identified the key features of enhancers that mediate differential responses to Toll-like receptor (TLR)-stimulation. We characterized the TLR3- and TLR9-induced programs and enhancers in CD8+ dendritic cells.The relevance of these features has been confirmed via machine learning application and by mapping SRTF-binding.
Project description:Stimulus-specific gene expression programs are enabled by enhancers, on which stimulus-regulated transcription factors (SRTFs) can land in a cell type- and stimulus-dependent manner. In this study, we identified the key features of enhancers that mediate differential responses to Toll-like receptor (TLR)-stimulation. We characterized the TLR3- and TLR9-induced programs and enhancers in CD8+ dendritic cells.The relevance of these features has been confirmed via machine learning application and by mapping SRTF-binding.
Project description:We inflicted TBI to chemokine-deficient mouse lines in order to establish involvement of various signalling pathways that may be addressed therapeutically. Interacting chemokine pathways in brain regulate distinct inflammatory cells. Activated microglia are separate from invading phagocytes and dendritic cells. Findings show potential targets to interfere with specific inflammatory responses after brain injury.
Project description:In this study, we demonstrate that endosome-localized self RNA Rmrp directly binds to TLR3 and induces TLR3 dimerization in the early endosome but does not interact with endosome-localized TLR7, TLR8, TLR9 or cytoplasmic RNA sensor RIG-I under homeostatic conditions. Cryo-EM structure of Rmrp-TLR3 complex reveals a novel lapped conformation of TLR3 dimer engaged by Rmrp, which is distinct from the activation mechanism by dsRNA and the specific structural feature at the 3'-end of Rmrp is critical for its functional interaction with TLR3. Furthermore, K42 residue of TLR3 is essential for binding to Rmrp and subsequent dimerization. Rmrp dissociates from TLR3 following endosomal acidification, generating a matured TLR3 dimer which is primed for innate recognition and activation. Myeloid-cell deficiency of Rmrp reduces TLR3 dimerization and attenuates TLR3-mediated antiviral responses against influenza A both in vitro and in vivo.
Project description:In mammals, retinal damage is followed by Müller glia cell activation and proliferation. While retinal gliosis persists in adult mammals after an insult or disease, some vertebrates, including zebrafish, have the capacity to regenerate. We believe we are the first group to show that gliosis is a fibrotic-like process in mammals’ eyes caused by differential activation of canonical and non-canonical TGFβ signaling pathways.
Project description:ChIP-seq of NCoR1 was performed to identify binding sites of NCoR1 in TLR dependent manner. MutuDC1940 cell line were treated with TLR3 ligand poly(I:C) and combined stimulation of TLR9 (CpG-B), TLR3, and IFNg for 6hr.