About: Cellular sensing of extracellular purine nucleosides triggers an innate IFN-β response

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An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Cellular sensing of extracellular purine nucleosides triggers an innate IFN-β response
Creator	Jain, Mohit M M U N O L O G Y, I Benedict, Chris Dhanwani, Rekha Hedrick, Catherine Lenzi, Camille Linden, Joel Mathews, Ian Nilsson, Roland Pieters, Bartijn Romanov, Artem Sharma, Sonia Takahashi, Mariko Watrous, Jeramie
Source	PMC
abstract	Mechanisms linking immune sensing of DNA danger signals in the extracellular environment to innate pathways in the cytosol are poorly understood. Here, we identify a previously unidentified immune-metabolic axis by which cells respond to purine nucleosides and trigger a type I interferon-β (IFN-β) response. We find that depletion of ADA2, an ectoenzyme that catabolizes extracellular dAdo to dIno, or supplementation of dAdo or dIno stimulates IFN-β. Under conditions of reduced ADA2 enzyme activity, dAdo is transported into cells and undergoes catabolysis by the cytosolic isoenzyme ADA1, driving intracellular accumulation of dIno. dIno is a functional immunometabolite that interferes with the cellular methionine cycle by inhibiting SAM synthetase activity. Inhibition of SAM-dependent transmethylation drives epigenomic hypomethylation and overexpression of immune-stimulatory endogenous retroviral elements that engage cytosolic dsRNA sensors and induce IFN-β. We uncovered a previously unknown cellular signaling pathway that responds to extracellular DNA–derived metabolites, coupling nucleoside catabolism by adenosine deaminases to cellular IFN-β production.
has issue date	2020-07-22(xsd:dateTime)
bibo:doi	10.1126/sciadv.aba3688
has license	cc-by-nc
sha1sum (hex)	4d16f1879ca8db15451d0b2d80fec438aeaf621f
schema:url	https://doi.org/10.1126/sciadv.aba3688
resource representing a document's title	Cellular sensing of extracellular purine nucleosides triggers an innate IFN-β response
has PubMed Central identifier	PMC7375821
schema:publication	Sci Adv
resource representing a document's body	covid:4d16f1879ca8db15451d0b2d80fec438aeaf621f#body_text
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