Matches in SemOpenAlex for { <https://semopenalex.org/work/W2904503476> ?p ?o ?g. }
Showing items 1 to 83 of
83
with 100 items per page.
- W2904503476 abstract "Author(s): York, Autumn Gabrielle | Advisor(s): Bensinger, Steven J | Abstract: Cellular lipid requirements are achieved through a combination of biosynthesis and import programs. To date, the molecular mechanisms that regulate whether a cell preferentially scavenges or synthesizes lipids is not well understood, particularly in non-metabolic tissues, such as immune cells. Perturbations in fatty acid and cholesterol homeostasis have been observed in response to a number of viral and microbial infections, leading us to ask if signaling through immune receptors could influence the cellular programs that regulate lipid homeostasis in macrophage. Using mass spectrometry and isotope tracer analysis, we find that activation of Toll-like Receptors (TLRs) can broadly promote a lipid-scavenging program, however, only select TLRs can specifically limit de novo synthesis of both fatty acids and cholesterol. We find that TLR- and virus-mediated production of type I interferon is responsible for inhibition of flux through the lipid biosynthetic program, resulting in a shift in macrophage metabolism to favor lipid import over synthesis. Genetically enforcing this metabolic shift in macrophages is sufficient to render mice resistant to viral challenge, demonstrating the importance of reprogramming the balance of these two metabolic pathways in vivo. Unexpectedly, mechanistic studies reveal that limiting flux through the cholesterol biosynthetic pathway spontaneously engages a type I IFN response in a STING-dependent manner. The upregulation of type I IFNs was traced to a decrease in the pool size of synthesized cholesterol, and replenishing cells with free cholesterol could inhibit STING-mediated production of type I IFNs. Taken together, these data support a model where perturbations in cholesterol biosynthetic flux intrinsically influence the STING signaling cascade and provide a molecular mechanism linking cholesterol homeostasis with type I IFN-mediated inflammation. In sum, these studies delineate a metabolic-inflammatory circuit that links perturbations in cholesterol biosynthesis with activation of innate immunity." @default.
- W2904503476 created "2018-12-22" @default.
- W2904503476 creator A5002168682 @default.
- W2904503476 date "2015-01-01" @default.
- W2904503476 modified "2023-09-27" @default.
- W2904503476 title "Identification of a cholesterol metabolic-type I interferon inflammatory circuit" @default.
- W2904503476 hasPublicationYear "2015" @default.
- W2904503476 type Work @default.
- W2904503476 sameAs 2904503476 @default.
- W2904503476 citedByCount "0" @default.
- W2904503476 crossrefType "journal-article" @default.
- W2904503476 hasAuthorship W2904503476A5002168682 @default.
- W2904503476 hasConcept C104317684 @default.
- W2904503476 hasConcept C110459506 @default.
- W2904503476 hasConcept C127561419 @default.
- W2904503476 hasConcept C167400880 @default.
- W2904503476 hasConcept C178790620 @default.
- W2904503476 hasConcept C185592680 @default.
- W2904503476 hasConcept C192989942 @default.
- W2904503476 hasConcept C202751555 @default.
- W2904503476 hasConcept C203014093 @default.
- W2904503476 hasConcept C2776178377 @default.
- W2904503476 hasConcept C2778163477 @default.
- W2904503476 hasConcept C2779244956 @default.
- W2904503476 hasConcept C2780072125 @default.
- W2904503476 hasConcept C4733338 @default.
- W2904503476 hasConcept C55493867 @default.
- W2904503476 hasConcept C62231903 @default.
- W2904503476 hasConcept C63932345 @default.
- W2904503476 hasConcept C68709404 @default.
- W2904503476 hasConcept C86339819 @default.
- W2904503476 hasConcept C86803240 @default.
- W2904503476 hasConcept C8891405 @default.
- W2904503476 hasConcept C95444343 @default.
- W2904503476 hasConceptScore W2904503476C104317684 @default.
- W2904503476 hasConceptScore W2904503476C110459506 @default.
- W2904503476 hasConceptScore W2904503476C127561419 @default.
- W2904503476 hasConceptScore W2904503476C167400880 @default.
- W2904503476 hasConceptScore W2904503476C178790620 @default.
- W2904503476 hasConceptScore W2904503476C185592680 @default.
- W2904503476 hasConceptScore W2904503476C192989942 @default.
- W2904503476 hasConceptScore W2904503476C202751555 @default.
- W2904503476 hasConceptScore W2904503476C203014093 @default.
- W2904503476 hasConceptScore W2904503476C2776178377 @default.
- W2904503476 hasConceptScore W2904503476C2778163477 @default.
- W2904503476 hasConceptScore W2904503476C2779244956 @default.
- W2904503476 hasConceptScore W2904503476C2780072125 @default.
- W2904503476 hasConceptScore W2904503476C4733338 @default.
- W2904503476 hasConceptScore W2904503476C55493867 @default.
- W2904503476 hasConceptScore W2904503476C62231903 @default.
- W2904503476 hasConceptScore W2904503476C63932345 @default.
- W2904503476 hasConceptScore W2904503476C68709404 @default.
- W2904503476 hasConceptScore W2904503476C86339819 @default.
- W2904503476 hasConceptScore W2904503476C86803240 @default.
- W2904503476 hasConceptScore W2904503476C8891405 @default.
- W2904503476 hasConceptScore W2904503476C95444343 @default.
- W2904503476 hasLocation W29045034761 @default.
- W2904503476 hasOpenAccess W2904503476 @default.
- W2904503476 hasPrimaryLocation W29045034761 @default.
- W2904503476 hasRelatedWork W1495031785 @default.
- W2904503476 hasRelatedWork W1655528082 @default.
- W2904503476 hasRelatedWork W1999650413 @default.
- W2904503476 hasRelatedWork W2010626816 @default.
- W2904503476 hasRelatedWork W2043174118 @default.
- W2904503476 hasRelatedWork W2192928441 @default.
- W2904503476 hasRelatedWork W2727529579 @default.
- W2904503476 hasRelatedWork W2791362302 @default.
- W2904503476 hasRelatedWork W2796410635 @default.
- W2904503476 hasRelatedWork W2889028407 @default.
- W2904503476 hasRelatedWork W2889333126 @default.
- W2904503476 hasRelatedWork W2936573240 @default.
- W2904503476 hasRelatedWork W2945607751 @default.
- W2904503476 hasRelatedWork W2991415497 @default.
- W2904503476 hasRelatedWork W3039906060 @default.
- W2904503476 hasRelatedWork W3044895467 @default.
- W2904503476 hasRelatedWork W3097083928 @default.
- W2904503476 hasRelatedWork W3202563871 @default.
- W2904503476 hasRelatedWork W3202941095 @default.
- W2904503476 hasRelatedWork W3207261217 @default.
- W2904503476 isParatext "false" @default.
- W2904503476 isRetracted "false" @default.
- W2904503476 magId "2904503476" @default.
- W2904503476 workType "article" @default.