Effect of Increased Lactate Dehydrogenase A Activity and Aerobic Glycolysis on the Proinflammatory Profile of Autoimmune CD8+ T Cells in Rheumatoid Arthritis
Objective CD8+ T cells contribute to rheumatoid arthritis (RA) by releasing proinflammatory and cytolytic mediators, even in a challenging hypoxic and nutrient‐poor microenvironment such as the synovial membrane. This study was undertaken to explore the mechanisms through which CD8+ T cells meet the...
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| Published in | Arthritis & rheumatology (Hoboken, N.J.) Vol. 72; no. 12; pp. 2050 - 2064 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Wiley Subscription Services, Inc
01.12.2020
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| Subjects | |
| Online Access | Get full text |
| ISSN | 2326-5191 2326-5205 2326-5205 |
| DOI | 10.1002/art.41420 |
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| Abstract | Objective
CD8+ T cells contribute to rheumatoid arthritis (RA) by releasing proinflammatory and cytolytic mediators, even in a challenging hypoxic and nutrient‐poor microenvironment such as the synovial membrane. This study was undertaken to explore the mechanisms through which CD8+ T cells meet their metabolic demands in the blood and synovial membrane of patients with RA.
Methods
Purified blood CD8+ T cells from patients with RA, patients with psoriatic arthritis (PsA), and patients with spondyloarthritis (SpA), as well as healthy control subjects, and CD8+ T cells from RA synovial membrane were stimulated in medium containing 13C‐labeled metabolic substrates in the presence or absence of metabolic inhibitors, under conditions of normoxia or hypoxia. The production of metabolic intermediates was quantified by 1H‐nuclear magnetic resonance. The expression of metabolic enzymes, transcription factors, and immune effector molecules was assessed at both the messenger RNA (mRNA) and protein levels. CD8+ T cell functional studies were performed.
Results
RA blood CD8+ T cells met their metabolic demands through aerobic glycolysis, production of uniformly 13C‐enriched lactate in the RA blood (2.6 to 3.7–fold higher than in patients with SpA, patients with PsA, and healthy controls; P < 0.01), and induction of glutaminolysis. Overexpression of Warburg effect–linked enzymes in all RA CD8+ T cell subsets maintained this metabolic profile, conferring to the cells the capacity to proliferate under hypoxia and low‐glucose conditions. In all RA CD8+ T cell subsets, lactate dehydrogenase A (LDHA) was overexpressed at the mRNA level (P < 0.03 versus controls; n = 6 per group) and protein level (P < 0.05 versus controls; n = 17 RA patients, n = 9 controls). In RA blood, inhibition of LDHA with FX11 led to reductions in lipogenesis, migration and proliferation of CD8+ T cells, and CD8+ T cell effector functions, while production of reactive oxygen species was increased by 1.5‐fold (P < 0.03 versus controls). Following inhibition of LDHA with FX11, RA CD8+ T cells lost their capacity to induce healthy B cells to develop a proinflammatory phenotype. Similar metabolic alterations were observed in RA CD8+ T cells from the synovial membrane.
Conclusion
Remodeling glucose and glutamine metabolism in RA CD8+ T cells by targeting LDHA activity can reduce the deleterious inflammatory and cytolytic contributions of these cells to the development of autoimmunity. |
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| AbstractList | CD8+ T cells contribute to rheumatoid arthritis (RA) by releasing proinflammatory and cytolytic mediators, even in a challenging hypoxic and nutrient-poor microenvironment such as the synovial membrane. This study was undertaken to explore the mechanisms through which CD8+ T cells meet their metabolic demands in the blood and synovial membrane of patients with RA.
Purified blood CD8+ T cells from patients with RA, patients with psoriatic arthritis (PsA), and patients with spondyloarthritis (SpA), as well as healthy control subjects, and CD8+ T cells from RA synovial membrane were stimulated in medium containing
C-labeled metabolic substrates in the presence or absence of metabolic inhibitors, under conditions of normoxia or hypoxia. The production of metabolic intermediates was quantified by
H-nuclear magnetic resonance. The expression of metabolic enzymes, transcription factors, and immune effector molecules was assessed at both the messenger RNA (mRNA) and protein levels. CD8+ T cell functional studies were performed.
RA blood CD8+ T cells met their metabolic demands through aerobic glycolysis, production of uniformly
C-enriched lactate in the RA blood (2.6 to 3.7-fold higher than in patients with SpA, patients with PsA, and healthy controls; P < 0.01), and induction of glutaminolysis. Overexpression of Warburg effect-linked enzymes in all RA CD8+ T cell subsets maintained this metabolic profile, conferring to the cells the capacity to proliferate under hypoxia and low-glucose conditions. In all RA CD8+ T cell subsets, lactate dehydrogenase A (LDHA) was overexpressed at the mRNA level (P < 0.03 versus controls; n = 6 per group) and protein level (P < 0.05 versus controls; n = 17 RA patients, n = 9 controls). In RA blood, inhibition of LDHA with FX11 led to reductions in lipogenesis, migration and proliferation of CD8+ T cells, and CD8+ T cell effector functions, while production of reactive oxygen species was increased by 1.5-fold (P < 0.03 versus controls). Following inhibition of LDHA with FX11, RA CD8+ T cells lost their capacity to induce healthy B cells to develop a proinflammatory phenotype. Similar metabolic alterations were observed in RA CD8+ T cells from the synovial membrane.
Remodeling glucose and glutamine metabolism in RA CD8+ T cells by targeting LDHA activity can reduce the deleterious inflammatory and cytolytic contributions of these cells to the development of autoimmunity. CD8+ T cells contribute to rheumatoid arthritis (RA) by releasing proinflammatory and cytolytic mediators, even in a challenging hypoxic and nutrient-poor microenvironment such as the synovial membrane. This study was undertaken to explore the mechanisms through which CD8+ T cells meet their metabolic demands in the blood and synovial membrane of patients with RA.OBJECTIVECD8+ T cells contribute to rheumatoid arthritis (RA) by releasing proinflammatory and cytolytic mediators, even in a challenging hypoxic and nutrient-poor microenvironment such as the synovial membrane. This study was undertaken to explore the mechanisms through which CD8+ T cells meet their metabolic demands in the blood and synovial membrane of patients with RA.Purified blood CD8+ T cells from patients with RA, patients with psoriatic arthritis (PsA), and patients with spondyloarthritis (SpA), as well as healthy control subjects, and CD8+ T cells from RA synovial membrane were stimulated in medium containing 13 C-labeled metabolic substrates in the presence or absence of metabolic inhibitors, under conditions of normoxia or hypoxia. The production of metabolic intermediates was quantified by 1 H-nuclear magnetic resonance. The expression of metabolic enzymes, transcription factors, and immune effector molecules was assessed at both the messenger RNA (mRNA) and protein levels. CD8+ T cell functional studies were performed.METHODSPurified blood CD8+ T cells from patients with RA, patients with psoriatic arthritis (PsA), and patients with spondyloarthritis (SpA), as well as healthy control subjects, and CD8+ T cells from RA synovial membrane were stimulated in medium containing 13 C-labeled metabolic substrates in the presence or absence of metabolic inhibitors, under conditions of normoxia or hypoxia. The production of metabolic intermediates was quantified by 1 H-nuclear magnetic resonance. The expression of metabolic enzymes, transcription factors, and immune effector molecules was assessed at both the messenger RNA (mRNA) and protein levels. CD8+ T cell functional studies were performed.RA blood CD8+ T cells met their metabolic demands through aerobic glycolysis, production of uniformly 13 C-enriched lactate in the RA blood (2.6 to 3.7-fold higher than in patients with SpA, patients with PsA, and healthy controls; P < 0.01), and induction of glutaminolysis. Overexpression of Warburg effect-linked enzymes in all RA CD8+ T cell subsets maintained this metabolic profile, conferring to the cells the capacity to proliferate under hypoxia and low-glucose conditions. In all RA CD8+ T cell subsets, lactate dehydrogenase A (LDHA) was overexpressed at the mRNA level (P < 0.03 versus controls; n = 6 per group) and protein level (P < 0.05 versus controls; n = 17 RA patients, n = 9 controls). In RA blood, inhibition of LDHA with FX11 led to reductions in lipogenesis, migration and proliferation of CD8+ T cells, and CD8+ T cell effector functions, while production of reactive oxygen species was increased by 1.5-fold (P < 0.03 versus controls). Following inhibition of LDHA with FX11, RA CD8+ T cells lost their capacity to induce healthy B cells to develop a proinflammatory phenotype. Similar metabolic alterations were observed in RA CD8+ T cells from the synovial membrane.RESULTSRA blood CD8+ T cells met their metabolic demands through aerobic glycolysis, production of uniformly 13 C-enriched lactate in the RA blood (2.6 to 3.7-fold higher than in patients with SpA, patients with PsA, and healthy controls; P < 0.01), and induction of glutaminolysis. Overexpression of Warburg effect-linked enzymes in all RA CD8+ T cell subsets maintained this metabolic profile, conferring to the cells the capacity to proliferate under hypoxia and low-glucose conditions. In all RA CD8+ T cell subsets, lactate dehydrogenase A (LDHA) was overexpressed at the mRNA level (P < 0.03 versus controls; n = 6 per group) and protein level (P < 0.05 versus controls; n = 17 RA patients, n = 9 controls). In RA blood, inhibition of LDHA with FX11 led to reductions in lipogenesis, migration and proliferation of CD8+ T cells, and CD8+ T cell effector functions, while production of reactive oxygen species was increased by 1.5-fold (P < 0.03 versus controls). Following inhibition of LDHA with FX11, RA CD8+ T cells lost their capacity to induce healthy B cells to develop a proinflammatory phenotype. Similar metabolic alterations were observed in RA CD8+ T cells from the synovial membrane.Remodeling glucose and glutamine metabolism in RA CD8+ T cells by targeting LDHA activity can reduce the deleterious inflammatory and cytolytic contributions of these cells to the development of autoimmunity.CONCLUSIONRemodeling glucose and glutamine metabolism in RA CD8+ T cells by targeting LDHA activity can reduce the deleterious inflammatory and cytolytic contributions of these cells to the development of autoimmunity. Objective CD8+ T cells contribute to rheumatoid arthritis (RA) by releasing proinflammatory and cytolytic mediators, even in a challenging hypoxic and nutrient‐poor microenvironment such as the synovial membrane. This study was undertaken to explore the mechanisms through which CD8+ T cells meet their metabolic demands in the blood and synovial membrane of patients with RA. Methods Purified blood CD8+ T cells from patients with RA, patients with psoriatic arthritis (PsA), and patients with spondyloarthritis (SpA), as well as healthy control subjects, and CD8+ T cells from RA synovial membrane were stimulated in medium containing 13C‐labeled metabolic substrates in the presence or absence of metabolic inhibitors, under conditions of normoxia or hypoxia. The production of metabolic intermediates was quantified by 1H‐nuclear magnetic resonance. The expression of metabolic enzymes, transcription factors, and immune effector molecules was assessed at both the messenger RNA (mRNA) and protein levels. CD8+ T cell functional studies were performed. Results RA blood CD8+ T cells met their metabolic demands through aerobic glycolysis, production of uniformly 13C‐enriched lactate in the RA blood (2.6 to 3.7–fold higher than in patients with SpA, patients with PsA, and healthy controls; P < 0.01), and induction of glutaminolysis. Overexpression of Warburg effect–linked enzymes in all RA CD8+ T cell subsets maintained this metabolic profile, conferring to the cells the capacity to proliferate under hypoxia and low‐glucose conditions. In all RA CD8+ T cell subsets, lactate dehydrogenase A (LDHA) was overexpressed at the mRNA level (P < 0.03 versus controls; n = 6 per group) and protein level (P < 0.05 versus controls; n = 17 RA patients, n = 9 controls). In RA blood, inhibition of LDHA with FX11 led to reductions in lipogenesis, migration and proliferation of CD8+ T cells, and CD8+ T cell effector functions, while production of reactive oxygen species was increased by 1.5‐fold (P < 0.03 versus controls). Following inhibition of LDHA with FX11, RA CD8+ T cells lost their capacity to induce healthy B cells to develop a proinflammatory phenotype. Similar metabolic alterations were observed in RA CD8+ T cells from the synovial membrane. Conclusion Remodeling glucose and glutamine metabolism in RA CD8+ T cells by targeting LDHA activity can reduce the deleterious inflammatory and cytolytic contributions of these cells to the development of autoimmunity. ObjectiveCD8+ T cells contribute to rheumatoid arthritis (RA) by releasing proinflammatory and cytolytic mediators, even in a challenging hypoxic and nutrient‐poor microenvironment such as the synovial membrane. This study was undertaken to explore the mechanisms through which CD8+ T cells meet their metabolic demands in the blood and synovial membrane of patients with RA.MethodsPurified blood CD8+ T cells from patients with RA, patients with psoriatic arthritis (PsA), and patients with spondyloarthritis (SpA), as well as healthy control subjects, and CD8+ T cells from RA synovial membrane were stimulated in medium containing 13C‐labeled metabolic substrates in the presence or absence of metabolic inhibitors, under conditions of normoxia or hypoxia. The production of metabolic intermediates was quantified by 1H‐nuclear magnetic resonance. The expression of metabolic enzymes, transcription factors, and immune effector molecules was assessed at both the messenger RNA (mRNA) and protein levels. CD8+ T cell functional studies were performed.ResultsRA blood CD8+ T cells met their metabolic demands through aerobic glycolysis, production of uniformly 13C‐enriched lactate in the RA blood (2.6 to 3.7–fold higher than in patients with SpA, patients with PsA, and healthy controls; P < 0.01), and induction of glutaminolysis. Overexpression of Warburg effect–linked enzymes in all RA CD8+ T cell subsets maintained this metabolic profile, conferring to the cells the capacity to proliferate under hypoxia and low‐glucose conditions. In all RA CD8+ T cell subsets, lactate dehydrogenase A (LDHA) was overexpressed at the mRNA level (P < 0.03 versus controls; n = 6 per group) and protein level (P < 0.05 versus controls; n = 17 RA patients, n = 9 controls). In RA blood, inhibition of LDHA with FX11 led to reductions in lipogenesis, migration and proliferation of CD8+ T cells, and CD8+ T cell effector functions, while production of reactive oxygen species was increased by 1.5‐fold (P < 0.03 versus controls). Following inhibition of LDHA with FX11, RA CD8+ T cells lost their capacity to induce healthy B cells to develop a proinflammatory phenotype. Similar metabolic alterations were observed in RA CD8+ T cells from the synovial membrane.ConclusionRemodeling glucose and glutamine metabolism in RA CD8+ T cells by targeting LDHA activity can reduce the deleterious inflammatory and cytolytic contributions of these cells to the development of autoimmunity. |
| Author | Carvalho, Rui A. Giese, Thomas Sandhoff, Roger Souto‐Carneiro, M. Margarida Kraus, Franziska V. Meyer, André P. Kriegsmann, Mark Carvalho, Lina Jennemann, Richard Klika, Karel D. Eckstein, Volker Abreu, Mónica T. Saffrich, Rainer Tykocinski, Lars Lorenz, Hanns‐Martin |
| Author_xml | – sequence: 1 givenname: M. Margarida orcidid: 0000-0001-6923-0590 surname: Souto‐Carneiro fullname: Souto‐Carneiro, M. Margarida email: margarida.souto-carneiro@med.uni-heidelberg.de organization: University Hospital Heidelberg – sequence: 2 givenname: Karel D. surname: Klika fullname: Klika, Karel D. organization: German Cancer Research Center – sequence: 3 givenname: Mónica T. surname: Abreu fullname: Abreu, Mónica T. organization: University of Coimbra – sequence: 4 givenname: André P. surname: Meyer fullname: Meyer, André P. organization: University Hospital Freiburg – sequence: 5 givenname: Rainer surname: Saffrich fullname: Saffrich, Rainer organization: University Hospital Heidelberg, Heidelberg, Germany, and Deutsches Rotes Kreuz Baden‐Württemberg–Hessen – sequence: 6 givenname: Roger surname: Sandhoff fullname: Sandhoff, Roger organization: German Cancer Research Center – sequence: 7 givenname: Richard surname: Jennemann fullname: Jennemann, Richard organization: German Cancer Research Center – sequence: 8 givenname: Franziska V. surname: Kraus fullname: Kraus, Franziska V. organization: University Hospital Heidelberg – sequence: 9 givenname: Lars surname: Tykocinski fullname: Tykocinski, Lars organization: University Hospital Heidelberg – sequence: 10 givenname: Volker surname: Eckstein fullname: Eckstein, Volker organization: University Hospital Heidelberg – sequence: 11 givenname: Lina surname: Carvalho fullname: Carvalho, Lina organization: University of Coimbra – sequence: 12 givenname: Mark surname: Kriegsmann fullname: Kriegsmann, Mark organization: University Hospital Heidelberg – sequence: 13 givenname: Thomas surname: Giese fullname: Giese, Thomas organization: University of Heidelberg – sequence: 14 givenname: Hanns‐Martin surname: Lorenz fullname: Lorenz, Hanns‐Martin organization: University Hospital Heidelberg – sequence: 15 givenname: Rui A. surname: Carvalho fullname: Carvalho, Rui A. organization: University of Coimbra |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32602217$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1126/scitranslmed.aad7151 10.4049/jimmunol.166.4.2878 10.1002/art.38376 10.1016/j.celrep.2014.07.053 10.1183/09031936.96.09081736 10.1002/art.40939 10.1002/art.27767 10.1084/jem.20130252 10.1016/j.it.2014.12.005 10.1093/rheumatology/kem279 10.1038/nature08097 10.1038/s41467-018-05044-4 10.1038/s41556-017-0002-2 10.1172/JCI69589 10.1002/eji.201343751 10.1042/BJ20081386 10.1186/s12860-016-0104-x 10.3389/fimmu.2018.01973 10.1002/art.38941 10.1186/ar2718 10.4049/jimmunol.174.1.533 10.1002/art.39608 10.1084/jem.20160061 10.1002/art.1780350804 10.1016/j.immuni.2011.12.007 10.1016/j.autrev.2005.04.012 10.1002/art.27729 10.1152/physrev.00011.2015 10.1002/art.38273 10.1146/annurev-cellbio-092910-154237 10.1038/ni.3808 10.1002/art.40218 10.1038/ni.2687 10.3389/fimmu.2018.02736 10.1016/j.celrep.2016.09.045 10.1002/1529-0131(200109)44:9<2038::AID-ART353>3.0.CO;2-1 10.1126/science.1242454 10.3389/fonc.2018.00331 10.1073/pnas.1407717111 10.1002/art.38015 10.1136/annrheumdis-2014-206119 10.4049/jimmunol.1302985 10.1038/ni.2714 10.1126/science.1250684 10.1073/pnas.91.11.4854 |
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| References | 2001; 166 2015; 36 2019; 71 2005; 174 2013; 65 2017; 69 2013; 43 2013; 123 2013; 342 2016; 75 2016; 96 1992; 35 2014; 192 2001; 44 2012; 36 2016; 17 2014; 111 2009; 417 2018; 20 2010; 62 2014; 66 2015; 67 2009; 11 2018; 9 2018; 8 2013; 14 2008; 47 2013; 210 2011; 63 2005; 4 2017; 18 2009; 460 2016; 213 2011; 27 1994; 91 2014; 8 2014; 345 2016; 8 1996; 9 2016; 68 e_1_2_7_6_1 e_1_2_7_5_1 e_1_2_7_4_1 e_1_2_7_3_1 e_1_2_7_9_1 e_1_2_7_8_1 e_1_2_7_7_1 e_1_2_7_19_1 e_1_2_7_18_1 e_1_2_7_17_1 e_1_2_7_16_1 e_1_2_7_40_1 e_1_2_7_2_1 e_1_2_7_15_1 e_1_2_7_41_1 e_1_2_7_14_1 e_1_2_7_42_1 e_1_2_7_13_1 e_1_2_7_43_1 e_1_2_7_12_1 e_1_2_7_44_1 e_1_2_7_11_1 e_1_2_7_45_1 e_1_2_7_10_1 e_1_2_7_46_1 e_1_2_7_26_1 e_1_2_7_27_1 e_1_2_7_28_1 e_1_2_7_29_1 e_1_2_7_30_1 e_1_2_7_31_1 e_1_2_7_24_1 e_1_2_7_32_1 e_1_2_7_23_1 e_1_2_7_33_1 e_1_2_7_22_1 e_1_2_7_34_1 Hradilkova K (e_1_2_7_20_1) 2019; 71 e_1_2_7_21_1 e_1_2_7_35_1 e_1_2_7_36_1 e_1_2_7_37_1 e_1_2_7_38_1 e_1_2_7_39_1 Cammann C (e_1_2_7_25_1) 2016; 17 |
| References_xml | – volume: 9 start-page: 1736 year: 1996 end-page: 42 article-title: Usefulness of lactate dehydrogenase and its isoenzymes as indicators of lung damage or inflammation [review] publication-title: Eur Respir J – volume: 11 start-page: R84 year: 2009 article-title: Alterations in peripheral blood memory B cells in patients with active rheumatoid arthritis are dependent on the action of tumour necrosis factor publication-title: Arthritis Res Ther – volume: 9 start-page: 2755 year: 2018 article-title: Multi‐omics monitoring of drug response in rheumatoid arthritis in pursuit of molecular remission publication-title: Nature Commun – volume: 8 start-page: 1461 year: 2014 end-page: 74 article-title: Hexokinase 2‐mediated Warburg effect is required for PTEN‐ and p53‐deficiency‐driven prostate cancer growth publication-title: Cell Rep – volume: 460 start-page: 103 year: 2009 end-page: 7 article-title: Enhancing CD8 T‐cell memory by modulating fatty acid metabolism publication-title: Nature – volume: 4 start-page: 549 year: 2005 end-page: 54 article-title: B‐cell differentiation in the CNS of patients with multiple sclerosis publication-title: Autoimmun Rev – volume: 68 start-page: 1614 year: 2016 end-page: 26 article-title: Critical role of glucose metabolism in rheumatoid arthritis fibroblast‐like synoviocytes publication-title: Arthritis Rheumatol – volume: 210 start-page: 2119 year: 2013 end-page: 34 article-title: Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox balance in rheumatoid arthritis T cells publication-title: J Exp Med – volume: 9 start-page: 1973 year: 2018 article-title: Inhibition of glycolysis reduces disease severity in an autoimmune model of rheumatoid arthritis publication-title: Front Immunol – volume: 96 start-page: 409 year: 2016 end-page: 47 article-title: Molecular actions of glucocorticoids in cartilage and bone during health, disease, and steroid therapy [review] publication-title: Physiol Rev – volume: 67 start-page: 363 year: 2015 end-page: 71 article-title: CD8+ T cell profiles in patients with rheumatoid arthritis and their relationship to disease activity publication-title: Arthritis Rheumatol – volume: 44 start-page: 2038 year: 2001 end-page: 45 article-title: Epitope specificity of clonally expanded populations of CD8+ T cells found within the joints of patients with inflammatory arthritis publication-title: Arthritis Rheum – volume: 417 start-page: 1 year: 2009 end-page: 13 article-title: How mitochondria produce reactive oxygen species [review] publication-title: Biochem J – volume: 192 start-page: 3190 year: 2014 end-page: 9 article-title: Regulator of fatty acid metabolism, acetyl coenzyme A carboxylase 1, controls T cell immunity publication-title: J Immunol – volume: 342 start-page: 1242454 year: 2013 article-title: Fueling immunity: insights into metabolism and lymphocyte function [review] publication-title: Science – volume: 18 start-page: 1025 year: 2017 end-page: 34 article-title: Metabolic control of the scaffold protein TKS5 in tissue‐invasive, proinflammatory T cells publication-title: Nat Immunol – volume: 111 start-page: 15526 year: 2014 end-page: 31 article-title: Role of pyruvate kinase M2 in transcriptional regulation leading to epithelial‐mesenchymal transition publication-title: Proc Natl Acad Sci U S A – volume: 166 start-page: 2878 year: 2001 end-page: 86 article-title: Psoriatic arthritis joint fluids are characterized by CD8 and CD4 T cell clonal expansions appear antigen driven publication-title: J Immunol – volume: 43 start-page: 2797 year: 2013 end-page: 809 article-title: The who's who of T‐cell differentiation: human memory T‐cell subsets publication-title: Eur J Immunol – volume: 123 start-page: 4479 year: 2013 end-page: 88 article-title: Inhibiting glycolytic metabolism enhances CD8 T cell memory and antitumor function publication-title: J Clin Invest – volume: 66 start-page: 513 year: 2014 end-page: 22 article-title: Features of the synovium of individuals at risk of developing rheumatoid arthritis: implications for understanding preclinical rheumatoid arthritis publication-title: Arthritis Rheumatol – volume: 69 start-page: 2114 year: 2017 end-page: 23 article-title: Synovial immunophenotype and anti–citrullinated peptide antibodies in rheumatoid arthritis patients: relationship to treatment response and radiologic prognosis publication-title: Arthritis Rheumatol – volume: 91 start-page: 4854 year: 1994 end-page: 8 article-title: Tumor necrosis factor ɑ inhibits signaling from the insulin receptor publication-title: Proc Natl Acad Sci U S A – volume: 8 start-page: 331 year: 2018 article-title: Fructose 2,6‐bisphosphate in cancer cell metabolism [review] publication-title: Front Oncol – volume: 14 start-page: 1064 year: 2013 end-page: 72 article-title: Rapid effector function of memory CD8+ T cells requires an immediate‐early glycolytic switch publication-title: Nat Immunol – volume: 66 start-page: 1272 year: 2014 end-page: 81 article-title: Interleukin‐17+CD8+ T cells are enriched in the joints of patients with psoriatic arthritis and correlate with disease activity and joint damage progression publication-title: Arthritis Rheumatol – volume: 20 start-page: 21 year: 2018 end-page: 7 article-title: A Pck1‐directed glycogen metabolic program regulates formation and maintenance of memory CD8 T cells publication-title: Nat Cell Biol – volume: 63 start-page: 63 year: 2011 end-page: 72 article-title: V‐region gene analysis of locally defined synovial B and plasma cells reveals selected B cell expansion and accumulation of plasma cell clones in rheumatoid arthritis publication-title: Arthritis Rheum – volume: 75 start-page: 748 year: 2016 end-page: 54 article-title: Premature senescence of T‐cell subsets in axial spondyloarthritis publication-title: Ann Rheum Dis – volume: 35 start-page: 865 year: 1992 end-page: 73 article-title: High percentage of CD8+, Leu‐7+ cells in rheumatoid arthritis synovial fluid publication-title: Arthritis Rheum – volume: 36 start-page: 68 year: 2012 end-page: 78 article-title: Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development publication-title: Immunity – volume: 27 start-page: 441 year: 2011 end-page: 64 article-title: Aerobic glycolysis: meeting the metabolic requirements of cell proliferation publication-title: Ann Rev Cell Dev Biol – volume: 345 start-page: 1250684 year: 2014 article-title: mTOR‐ and HIF‐1ɑ‐mediated aerobic glycolysis as metabolic basis for trained immunity publication-title: Science – volume: 174 start-page: 533 year: 2005 end-page: 41 article-title: Genetic interactions in Eae2 control collagen‐induced arthritis and the CD4+/CD8+ T cell ratio publication-title: J Immunol – volume: 8 start-page: 331ra38 year: 2016 article-title: Restoring oxidant signaling suppresses proarthritogenic T cell effector functions in rheumatoid arthritis publication-title: Sci Transl Med – volume: 62 start-page: 2953 year: 2010 end-page: 62 article-title: Monoclonal anti‐CD8 therapy induces disease amelioration in the K/BxN mouse model of spontaneous chronic polyarthritis publication-title: Arthritis Rheum – volume: 14 start-page: 1173 year: 2013 end-page: 82 article-title: Hypoxia‐inducible factors enhance the effector responses of CD8+ T cells to persistent antigen publication-title: Nat Immunol – volume: 9 start-page: 2736 year: 2018 article-title: Naive CD8 T‐cells engage a versatile metabolic program upon activation in humans and differ energetically from memory CD8 T‐cells publication-title: Front Immunol – volume: 213 start-page: 1655 year: 2016 end-page: 62 article-title: GPR91 senses extracellular succinate released from inflammatory macrophages and exacerbates rheumatoid arthritis publication-title: J Exp Med – volume: 17 start-page: 28 year: 2016 article-title: Early changes in the metabolic profile of activated CD8 T cells publication-title: BMC Cell Biol – volume: 36 start-page: 81 year: 2015 end-page: 91 article-title: Fatty acid metabolism in the regulation of T cell function publication-title: Trends Immunol – volume: 65 start-page: 2201 year: 2013 end-page: 10 article-title: Premature cell senescence and T cell receptor–independent activation of CD8+ T cells in juvenile idiopathic arthritis publication-title: Arthritis Rheum – volume: 47 start-page: 249 year: 2008 end-page: 55 article-title: Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis [review] publication-title: Rheumatology (Oxford) – volume: 17 start-page: 821 year: 2016 end-page: 36 article-title: Addiction to coupling of the Warburg effect with glutamine catabolism in cancer cells publication-title: Cell Rep – volume: 71 start-page: 756 year: 2019 end-page: 65 article-title: Regulation of fatty acid oxidation by Twist 1 in the metabolic adaptation of T helper lymphocytes to chronic inflammation publication-title: Arthritis Rheumatol – ident: e_1_2_7_19_1 doi: 10.1126/scitranslmed.aad7151 – ident: e_1_2_7_40_1 doi: 10.4049/jimmunol.166.4.2878 – ident: e_1_2_7_41_1 doi: 10.1002/art.38376 – ident: e_1_2_7_26_1 doi: 10.1016/j.celrep.2014.07.053 – ident: e_1_2_7_32_1 doi: 10.1183/09031936.96.09081736 – volume: 71 start-page: 756 year: 2019 ident: e_1_2_7_20_1 article-title: Regulation of fatty acid oxidation by Twist 1 in the metabolic adaptation of T helper lymphocytes to chronic inflammation publication-title: Arthritis Rheumatol doi: 10.1002/art.40939 – ident: e_1_2_7_38_1 doi: 10.1002/art.27767 – ident: e_1_2_7_21_1 doi: 10.1084/jem.20130252 – ident: e_1_2_7_16_1 doi: 10.1016/j.it.2014.12.005 – ident: e_1_2_7_24_1 doi: 10.1093/rheumatology/kem279 – ident: e_1_2_7_12_1 doi: 10.1038/nature08097 – ident: e_1_2_7_29_1 doi: 10.1038/s41467-018-05044-4 – ident: e_1_2_7_37_1 doi: 10.1038/s41556-017-0002-2 – ident: e_1_2_7_28_1 doi: 10.1172/JCI69589 – ident: e_1_2_7_31_1 doi: 10.1002/eji.201343751 – ident: e_1_2_7_34_1 doi: 10.1042/BJ20081386 – volume: 17 start-page: 28 year: 2016 ident: e_1_2_7_25_1 article-title: Early changes in the metabolic profile of activated CD8+ T cells publication-title: BMC Cell Biol doi: 10.1186/s12860-016-0104-x – ident: e_1_2_7_46_1 doi: 10.3389/fimmu.2018.01973 – ident: e_1_2_7_3_1 doi: 10.1002/art.38941 – ident: e_1_2_7_39_1 doi: 10.1186/ar2718 – ident: e_1_2_7_6_1 doi: 10.4049/jimmunol.174.1.533 – ident: e_1_2_7_44_1 doi: 10.1002/art.39608 – ident: e_1_2_7_45_1 doi: 10.1084/jem.20160061 – ident: e_1_2_7_2_1 doi: 10.1002/art.1780350804 – ident: e_1_2_7_11_1 doi: 10.1016/j.immuni.2011.12.007 – ident: e_1_2_7_43_1 doi: 10.1016/j.autrev.2005.04.012 – ident: e_1_2_7_7_1 doi: 10.1002/art.27729 – ident: e_1_2_7_22_1 doi: 10.1152/physrev.00011.2015 – ident: e_1_2_7_8_1 doi: 10.1002/art.38273 – ident: e_1_2_7_15_1 doi: 10.1146/annurev-cellbio-092910-154237 – ident: e_1_2_7_18_1 doi: 10.1038/ni.3808 – ident: e_1_2_7_9_1 doi: 10.1002/art.40218 – ident: e_1_2_7_17_1 doi: 10.1038/ni.2687 – ident: e_1_2_7_36_1 doi: 10.3389/fimmu.2018.02736 – ident: e_1_2_7_33_1 doi: 10.1016/j.celrep.2016.09.045 – ident: e_1_2_7_5_1 doi: 10.1002/1529-0131(200109)44:9<2038::AID-ART353>3.0.CO;2-1 – ident: e_1_2_7_10_1 doi: 10.1126/science.1242454 – ident: e_1_2_7_30_1 doi: 10.3389/fonc.2018.00331 – ident: e_1_2_7_27_1 doi: 10.1073/pnas.1407717111 – ident: e_1_2_7_4_1 doi: 10.1002/art.38015 – ident: e_1_2_7_42_1 doi: 10.1136/annrheumdis-2014-206119 – ident: e_1_2_7_35_1 doi: 10.4049/jimmunol.1302985 – ident: e_1_2_7_13_1 doi: 10.1038/ni.2714 – ident: e_1_2_7_14_1 doi: 10.1126/science.1250684 – ident: e_1_2_7_23_1 doi: 10.1073/pnas.91.11.4854 |
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CD8+ T cells contribute to rheumatoid arthritis (RA) by releasing proinflammatory and cytolytic mediators, even in a challenging hypoxic and... CD8+ T cells contribute to rheumatoid arthritis (RA) by releasing proinflammatory and cytolytic mediators, even in a challenging hypoxic and nutrient-poor... ObjectiveCD8+ T cells contribute to rheumatoid arthritis (RA) by releasing proinflammatory and cytolytic mediators, even in a challenging hypoxic and... |
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| SubjectTerms | Adolescent Adult Aged Arthritis Arthritis, Psoriatic - immunology Arthritis, Psoriatic - metabolism Arthritis, Rheumatoid - immunology Arthritis, Rheumatoid - metabolism Autoimmunity Blood CD8 antigen CD8-Positive T-Lymphocytes - metabolism Cell proliferation Dehydrogenase Dehydrogenases Enzymes Female Glucose Glucose metabolism Glutamine Glycolysis Glycolysis - physiology Humans Hypoxia Inflammation Inflammation - metabolism Inflammatory diseases Intermediates L-Lactate dehydrogenase Lactate dehydrogenase Lactate Dehydrogenase 5 - metabolism Lactic acid Lipogenesis Lymphocytes Lymphocytes B Lymphocytes T Male Membranes Metabolism Middle Aged NMR Nuclear magnetic resonance Phenotypes Proteins Psoriatic arthritis Reactive oxygen species Rheumatic diseases Rheumatoid arthritis Spondylarthritis - immunology Spondylarthritis - metabolism Substrates Synovial membrane Transcription factors Young Adult |
| Title | Effect of Increased Lactate Dehydrogenase A Activity and Aerobic Glycolysis on the Proinflammatory Profile of Autoimmune CD8+ T Cells in Rheumatoid Arthritis |
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