A new model of innate immune response regulation by the nucleotide metabolism – INNATENUCLEOTIDES

-real time quantitative PCR to quantify the levels of expression of somme genes of the interferon response
-RNA interference (siRNAs and shNAs) to deplete cells of somme proteins of interest
-transductions to express some proteins of interest in cells
-CRISPR/Cas9 technology to knockout somme cellular genes
-construction of a mouse model with the knockout of the cytidine deaminase gene

Confidential

Identification of new mechanisms involved in host defense and understanding of the functional relationship between DNA damage, replication stress and innate immunity.

An article will be written in the near future

Innate immunity, an essential arm of the immune system, must be kept under tight control to avoid adverse effects to the host, such as immunodeficiency or autoimmunity. Although the metabolism of cellular nucleotides and DNA repair was recently linked to the regulation of innate immune responses, the mechanisms underlying its deregulation are unclear. We found that in human cells presenting a specific defect in DNA repair and nucleotide metabolism, an innate immune response is constitutively activated. Our project aims (1) to characterize the early events leading to the innate immune response in cells presenting a nucleotide pool defect, (2) to evaluate the role of nucleotide pool disequilibrium in inducing innate immunity in cellular and in vivo models, and (3) to investigate the possible relationship between replication stress and innate immunity. Results from these studies will shed light of novel mechanisms implicated in host defense, health and disease.