Community Research and Development Information Service - CORDIS


TLR-lncRNAs — Result In Brief

Project ID: 322089
Funded under: FP7-PEOPLE
Country: Israel
Domain: Health, Fundamental Research

Non-coding RNAs regulate immune responses

Immune cells protect the body from invading pathogens through responses executed largely through the induction of specific gene programmes.
Non-coding RNAs regulate immune responses
The toll-like receptor (TLR) family of molecules are pattern recognition receptors that are instrumental for immune responses against a variety of microbes. Expressed on dendritic cells, recent studies implicate TLRs in a diverse set of diseases including diabetes, inflammatory bowel disease, lupus and rheumatoid arthritis. Interaction of TLR with pathogen-specific components initiates a transcriptional response, which activates thousands of genes necessary to alert the adaptive immune system and eliminate the pathogenic threat.

Although upstream signalling components that mediate pathogen-sensing by TLRs are well established, relatively little is known about the downstream transcriptional cascades that directly control specific gene expression. It is important to comprehend the molecular mechanisms underlying the regulation of these dynamic gene responses. Towards this goal, the EU-funded TLR-LNCRNAS (Systematic elucidation of the regulatory roles of large non-coding RNAs in the toll-like receptor pathway) project systematically measured the regulatory role of transcriptional regulators involved in the dendritic cell response to TLR activation.

Scientists developed novel single-cell genomic technologies for identifying regulatory regions and large non-coding RNAs (lncRNAs) involved in regulating immune outcome following pathogen exposure. Combined with models for haematopoiesis and immune response, these technologies provided important insight into diverse regulatory mechanisms underlying haematopoietic development and immune decisions. They identified a subset of lncRNAs, which regulated gene expression in innate immune cells upon pathogen stimuli. For long, lncRNAs were considered to be transcriptional noise but emerging evidence supports their involvement in various physiological processes.

Overall, the advanced tools generated during the TLR-LNCRNAS project allowed the delineation of diverse regulatory mechanisms implicated in haematopoietic development and immune decisions. Novel insight was also generated into immune checkpoints with a role in pathologies ranging from cancer to neurological, haematopoiesis-related diseases and diabetes.

Long-term these systematic studies are expected to bridge the gap between basic regulatory mechanisms and their physiological in vivo consequences in health and disease.

Related information


Life Sciences


TLR, dendritic cells, transcription, TLR-LNCRNAS, lncRNAs
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