ArticlebioRxiv : the preprint server for biology2025
Metabolic Adaptations Rewire CD4 T Cells in a Subset-Specific Manner in Human Critical Illness with and without Sepsis.
Matthew T Stier, Allison E Sewell, Erin L Mwizerwa, Chooi Ying Sim, Samantha M Tanner, Casey M Nichols, Heather H Durai, Erin Q Jennings, Paul Lindau, Erin M Wilfong and 4 more
Abstract readPreprint
In one paragraphArticle in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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2 · The registryThe trial behind it
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
14 authors.
Matthew T StierDivision of Allergy, Pulmonary & Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.ORCID 0000-0003-3928-1682 Allison E SewellDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States.ORCID 0000-0001-7077-0762 Erin L MwizerwaDivision of Allergy, Pulmonary & Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
Chooi Ying SimDivision of Allergy, Pulmonary & Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
Samantha M TannerDivision of Allergy, Pulmonary & Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
Casey M NicholsDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States.
Heather H DuraiDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States.
Erin Q JenningsDivision of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.ORCID 0000-0002-6991-6098 Paul LindauDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.ORCID 0000-0003-4392-1232 Erin M WilfongDivision of Allergy, Pulmonary & Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.ORCID 0000-0002-6584-1578 Dawn C NewcombDivision of Allergy, Pulmonary & Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.ORCID 0000-0003-2592-9433 Julie A BastaracheDivision of Allergy, Pulmonary & Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.ORCID 0000-0003-0458-6507 Lorraine B WareDivision of Allergy, Pulmonary & Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.ORCID 0000-0002-9429-4702 Jeffrey C RathmellVanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN, United States.ORCID 0000-0002-4106-3396 Funding
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007347 · NIGMS · VANDERBILT UNIVERSITY · PI WILLIAMS, CHRISTOPHER S. · 1985 to 2023
$26.3MInstitutional Career Development CoreKL2TR002245 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Julie A. Bastarache · 2017 to 2026
$9.3MBIOCHEMICAL &CHEMICAL TRAINING FOR CANCER RESEARCHT32CA009582 · NCI · VANDERBILT UNIVERSITY · PI David K Cortez · 1987 to 2026
$8.8MEnhancing Treg Therapeutic Efficacy in GVHDR01HL118979 · NHLBI · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, HIPPEN, KELI L · 2014 to 2025
$6.7MInterdisciplinary Training Program in Lung ResearchT32HL094296 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Ray Stokes Peebles · 2008 to 2026
$6.3MMedical Scientist Training ProgramT32GM152284 · NIGMS · VANDERBILT UNIVERSITY · PI Christopher S. Williams · 2024 to 2026
$4.8MExploiting metabolic vulnerabilities of CD4 T cell subsets to control inflammatory diseaseR01DK105550 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jeffrey C Rathmell · 2015 to 2026
$4.7MApplying Innovative Lung Mapping Strategies to Understand Alveolar Capillary Barrier Permeability in ARDSR35HL150783 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Julie A. Bastarache · 2020 to 2026
$4.6MInterdisciplinary Training in Rheumatic DiseasesT32AR059039 · NIAMS · VANDERBILT UNIVERSITY · PI Tracy Minan Frech, AMY S MAJOR · 2010 to 2026
$4.3MTargeting TH17 cell metabolism in steroid resistanceR01HL136664 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI NEWCOMB, DAWN C, RATHMELL, JEFFREY C. · 2017 to 2024
$4.2MNeuroinflammatory mechanisms underlying sepsis-induced cognitive dysfunctionRF1AG075341 · NIA · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BASTARACHE, JULIE A., HARRISON, FIONA EDITH · 2022 to 2025
$3.3MTargeting Tfh Cell Metabolic Regulation in SLE and SLE-Associated AtherosclerosisR01AI153167 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MAJOR, AMY S, RATHMELL, JEFFREY C. · 2020 to 2024
$2.8MNCATS NIH HHS KL2 TR002245NCI NIH HHS T32 CA009582NHLBI NIH HHS R01 HL118979NHLBI NIH HHS R01 HL136664NHLBI NIH HHS R01 HL158906NHLBI NIH HHS R01 HL164937NHLBI NIH HHS R35 HL150783NHLBI NIH HHS T32 HL094296NIAID NIH HHS R01 AI153167NIAMS NIH HHS K08 AR080808NIAMS NIH HHS T32 AR059039NIA NIH HHS RF1 AG075341NIDDK NIH HHS R01 DK105550NIGMS NIH HHS R21 GM144915NIGMS NIH HHS R33 GM144915NIGMS NIH HHS T32 GM007347NIGMS NIH HHS T32 GM152284
6 · The paper itselfAbstract
Host immunity in sepsis has features of hyperinflammation together with progressive immunosuppression, particularly among CD4 T cells, that can predispose to secondary infections and ineffectual organ recovery. Metabolic and immunologic dysfunction are archetypal findings in critically ill patients with sepsis, but whether these factors are mechanistically linked remains incompletely defined. We characterized functional metabolic properties of human CD4 T cells from critically ill patients with and without sepsis and healthy adults. CD4 T cells in critical illness showed increased subset-specific metabolic plasticity, with regulatory T cells (Tregs) acquiring glycolytic capacity that stabilized suppressive markers FOXP3 and TIGIT and correlated with clinical illness severity. Single-cell transcriptomics identified differential kynurenine metabolism in Tregs, which was validated
Identifiers
PMID39975258
PMCPMC11838299
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