Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313407968> ?p ?o ?g. }
Showing items 1 to 72 of
72
with 100 items per page.
- W4313407968 endingPage "158.14" @default.
- W4313407968 startingPage "158.14" @default.
- W4313407968 abstract "Abstract In diseases such as multiple sclerosis and autoimmune encephalitides, activated CD8+ cytotoxic T cells infiltrate the brain and are found in clonally expanded clusters that outnumber CD4+ cells in progressive stages of disease. At present, the pathophysiological role of these cells is poorly understood and therapeutic strategies for preventing or ameliorating autoinflammatory disease progression are limited. T cells exhibit profound metabolic reprogramming that facilitates the energetic and proliferative demands of effector T cells. Key metabolic pathways in this reprogramming include upregulation of glycolysis and the pentose phosphate pathway (PPP). Here we show that 1) pharmacologic inhibition of the PPP suppresses effector phenotype acquisition and proinflammatory cytokine secretion by CD8+ T cells; 2) engagement of the PPP is enhanced by pharmacologic Nrf2 activation, implicating reactive oxygen species-induced activation as a transcriptional regulator of PPP-dependent immune activation; 3) Nrf2-driven PPP flux promotes the acquisition of specific CD8+ effector phenotypes; 4) limiting the metabolic flux of glucose-derived metabolites through the PPP prevents CD8+ T cell-mediated injury of neurons expressing cognate antigen and preserves their electrophysiological function; and 5) pharmacologic inhibition of the PPP in B6 mice at symptom onset is sufficient to delay and ameliorate motor disability in the MOG EAE preclinical model of MS. Overall, these results underscore the potential of immunometabolic therapies to limit T cell mediated injury in autoinflammatory and autoimmune diseases across organ systems including the prevention of neurologic deficits in patients with T cell driven neurologic disease. This work was supported by the NIH (R01NS115126 to CLH; T32GM065841 to EMG), the Mayo Clinic Graduate School of Biomedical Sciences, the Mayo Clinic Center for MS and Autoimmune Neurology, and generous donations from Eugene and Marcia Applebaum, Donald J. and Frances I. Herdrich, Bob and Loralee Marvin, and Rob and Debbie Mudge." @default.
- W4313407968 created "2023-01-06" @default.
- W4313407968 creator A5035449588 @default.
- W4313407968 creator A5047141595 @default.
- W4313407968 creator A5064393678 @default.
- W4313407968 date "2022-05-01" @default.
- W4313407968 modified "2023-10-16" @default.
- W4313407968 title "Inhibition of the Pentose Phosphate Pathway in Cytotoxic T Lymphocytes Preserves Neuronal Function and Ameliorates Neuroinflammatory Disease" @default.
- W4313407968 doi "https://doi.org/10.4049/jimmunol.208.supp.158.14" @default.
- W4313407968 hasPublicationYear "2022" @default.
- W4313407968 type Work @default.
- W4313407968 citedByCount "0" @default.
- W4313407968 crossrefType "journal-article" @default.
- W4313407968 hasAuthorship W4313407968A5035449588 @default.
- W4313407968 hasAuthorship W4313407968A5047141595 @default.
- W4313407968 hasAuthorship W4313407968A5064393678 @default.
- W4313407968 hasConcept C104317684 @default.
- W4313407968 hasConcept C127561419 @default.
- W4313407968 hasConcept C1491633281 @default.
- W4313407968 hasConcept C154317977 @default.
- W4313407968 hasConcept C167672396 @default.
- W4313407968 hasConcept C20251656 @default.
- W4313407968 hasConcept C202751555 @default.
- W4313407968 hasConcept C203014093 @default.
- W4313407968 hasConcept C2776090121 @default.
- W4313407968 hasConcept C3409486 @default.
- W4313407968 hasConcept C502942594 @default.
- W4313407968 hasConcept C51785407 @default.
- W4313407968 hasConcept C55493867 @default.
- W4313407968 hasConcept C62231903 @default.
- W4313407968 hasConcept C77255625 @default.
- W4313407968 hasConcept C86803240 @default.
- W4313407968 hasConcept C8891405 @default.
- W4313407968 hasConcept C95444343 @default.
- W4313407968 hasConceptScore W4313407968C104317684 @default.
- W4313407968 hasConceptScore W4313407968C127561419 @default.
- W4313407968 hasConceptScore W4313407968C1491633281 @default.
- W4313407968 hasConceptScore W4313407968C154317977 @default.
- W4313407968 hasConceptScore W4313407968C167672396 @default.
- W4313407968 hasConceptScore W4313407968C20251656 @default.
- W4313407968 hasConceptScore W4313407968C202751555 @default.
- W4313407968 hasConceptScore W4313407968C203014093 @default.
- W4313407968 hasConceptScore W4313407968C2776090121 @default.
- W4313407968 hasConceptScore W4313407968C3409486 @default.
- W4313407968 hasConceptScore W4313407968C502942594 @default.
- W4313407968 hasConceptScore W4313407968C51785407 @default.
- W4313407968 hasConceptScore W4313407968C55493867 @default.
- W4313407968 hasConceptScore W4313407968C62231903 @default.
- W4313407968 hasConceptScore W4313407968C77255625 @default.
- W4313407968 hasConceptScore W4313407968C86803240 @default.
- W4313407968 hasConceptScore W4313407968C8891405 @default.
- W4313407968 hasConceptScore W4313407968C95444343 @default.
- W4313407968 hasIssue "1_Supplement" @default.
- W4313407968 hasLocation W43134079681 @default.
- W4313407968 hasOpenAccess W4313407968 @default.
- W4313407968 hasPrimaryLocation W43134079681 @default.
- W4313407968 hasRelatedWork W1513178816 @default.
- W4313407968 hasRelatedWork W1982722337 @default.
- W4313407968 hasRelatedWork W2015747966 @default.
- W4313407968 hasRelatedWork W2018916009 @default.
- W4313407968 hasRelatedWork W2098292655 @default.
- W4313407968 hasRelatedWork W2115186514 @default.
- W4313407968 hasRelatedWork W2153248803 @default.
- W4313407968 hasRelatedWork W2899988463 @default.
- W4313407968 hasRelatedWork W2901569396 @default.
- W4313407968 hasRelatedWork W4256638720 @default.
- W4313407968 hasVolume "208" @default.
- W4313407968 isParatext "false" @default.
- W4313407968 isRetracted "false" @default.
- W4313407968 workType "article" @default.