2015206 Raw data.xlsx

<div>Dataset associated with Nature Medicine (2016), doi:10.1038/nm.4106</div><div><br></div><div>Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor</div><div><br></div><div>1. RNA-Sequencing data of astrocytes during late stage Experimental autoimmune encephalomyelitis (EAE experiments) as compared to naive mice</div><div><br></div><div>2. Nanostring data of astrocytes and microglia during EAE</div><div><br></div><div><br></div

Sanmarco et al., 2023.pdf

Dendritic cells (DCs) control the generation of self-reactive pathogenic T cells. Thus, DCs are considered attractive therapeutic targets for autoimmune diseases. Using single-cell and bulk transcriptional and metabolic analyses in combination with cell-specific gene perturbation studies we identified a negative feedback regulatory pathway that operates in DCs to limit immunopathology. Specifically, we found that lactate, produced by activated DCs and other immune cells, boosts NDUFA4L2 expression through a mechanism mediated by HIF-1a. NDUFA4L2 limits the production of mitochondrial reactive oxygen species that activate XBP1-driven transcriptional modules in DCs involved in the control of pathogenic autoimmune T cells. Moreover, we engineered a probiotic that produces lactate and suppresses T-cell autoimmunity in the central nervous system via the activation of HIF-1a/NDUFA4L2 signaling in DCs. In summary, we identified an immunometabolic pathway that regulates DC function, and developed a synthetic probiotic for its therapeutic activation. </p