ArticleNature immunology2024
Age-related epithelial defects limit thymic function and regeneration.
Erratum issuedAbstract read
In one paragraph
Article in Nature immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 78 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 1 pooled it
–field-weighted citation impact
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Can Non-Thymomatous Late-Onset Myasthenia Gravis Benefit From Thymectomy? A Systematic Review and Meta-Analysis.European journal of neurology · 2025Pooled it
- Aire and Fezf2 Shape the Medullary Thymic Epithelial Cell Immunopeptidome for Central Tolerance.Immunology · 2026Review
- Dysregulated thymus-ovary axis promotes virtual memory T cell polarization to aggravate PMOS pathology.Cellular & molecular immunology · 2026Article
- Mesenchymal cells rebuild the thymus.Nature biotechnology · 2026Article
- Lymph node contraction links sex-biased naive CD8Nature aging · 2026Article
- The role of senescence in kidney ageing, injury and fibrosis.Nature reviews. Nephrology · 2026Review
- Review
- The Thymic Microenvironment Shapes Age-Related Qualitative Changes in the TCR Repertoire.Aging cell · 2026Article
- [Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Article
- Article
- Article
- Analysis of Human Thymopoiesis Reveals Rapid Postnatal Remodeling of Thymocytes Within the First 3 Months of Life.European journal of immunology · 2026Article
- Fibroblast-driven collagen expansion and altered thymic medullary niches in 22q11.2 deletion syndrome.Journal of human immunity · 2026Article
- What Do We Know About Immune System Aging from Human and Animal Studies?International journal of molecular sciences · 2026Review
- Clonal Analyses Reveal the Impact of Hematopoietic Stem and Progenitor Cell Aging on T Cell Development.Aging cell · 2026Article
- GW9508-Induced Activation of GPR40 in Thymic Epithelial Cells: A Therapeutic Strategy to Delay Thymic Aging.Aging cell · 2026Article
- ZFP36L1 and ZFP36L2 cooperatively regulate thymic epithelial cell function to prevent early-onset thymic involution.Cell death and differentiation · 2026Article
- Foxp1 controls Fezf2-dependent gene expression, mimetic mTEC diversity, and thymic central tolerance.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Aging diminishes thymic output, reduces naive T cells, promotes memory T-cell accumulation, and impairs thymic regeneration.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Article
- From Development to Aging: Dynamic Roles of the Thymic Medulla in T Cell Biology.Immunological reviews · 2026Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
38 authors.
Anastasia I Kousa *Program in Immunology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-4550-0389
Lorenz Jahn *Program in Immunology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-9880-7026
Kelin Zhao *The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Angel E FloresDepartment of Genetics, University of Georgia, Athens, GA, USA.
Dante AcenasTranslational Science and Therapeutics Division, and Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Emma LedererTranslational Science and Therapeutics Division, and Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0009-0008-4103-5388
Kimon V ArgyropoulosDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Andri L LemarquisProgram in Immunology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
David GranadierTranslational Science and Therapeutics Division, and Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Kirsten CooperTranslational Science and Therapeutics Division, and Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-0711-2713
Michael D'AndreaThe Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.ORCID http://orcid.org/0000-0002-2557-3628
Julie M SheridanThe Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.ORCID http://orcid.org/0000-0002-1478-3662
Jennifer TsaiProgram in Immunology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-9267-4584
Lisa SikkemaComputational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Amina LazrakProgram in Immunology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Katherine NicholsProgram in Immunology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nichole LeeProgram in Immunology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Romina GhaleProgram in Immunology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Florent MalardProgram in Immunology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Hana AndrlovaProgram in Immunology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Enrico VelardiDivision of Pediatric Hematology and Oncology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.ORCID http://orcid.org/0000-0001-8383-0453
Salma YoussefProgram in Immunology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0009-0005-3499-7755
Marina Burgos da SilvaProgram in Immunology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Melissa DocampoProgram in Immunology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Roshan SharmaComputational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Linas MazutisComputational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-5552-6427
Verena C WimmerThe Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Kelly L RogersThe Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.ORCID http://orcid.org/0000-0002-6755-0221
Susan DeWolfDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Brianna GipsonProgram in Immunology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0009-0005-5837-8676
Antonio L C GomesProgram in Immunology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Manu SettyComputational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-0344-2627
Dana Pe'erComputational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-9259-8817
Laura HaleHuman Vaccine Institute, Duke University, Durham, NC, USA.
Nancy R ManleyDepartment of Genetics, University of Georgia, Athens, GA, USA.
Daniel H D GrayThe Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. dgray@wehi.edu.au.ORCID http://orcid.org/0000-0002-8457-8242
Marcel R M van den BrinkProgram in Immunology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. mvandenbrink@coh.org.ORCID http://orcid.org/0000-0003-0696-4401
Jarrod A DudakovTranslational Science and Therapeutics Division, and Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA, USA. jdudakov@fredhutch.org.ORCID http://orcid.org/0000-0001-6220-5632
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MTranslational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Marian Esvelt · 1985 to 2026
$296.4MT LYMPHOCYTE SUBSET FUNCTION POST-TRANSPLANTATIONP01CA023766 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI PAMER, ERIC G. · 1985 to 2023
$59.0MThymic and Peripheral Aspects of T Cell Aging and RejuvenationP01AG052359 · NIA · UNIVERSITY OF ARIZONA · PI Laura P. Hale · 2017 to 2026
$23.5MTRAINING IN MOLECULAR AND CELLULAR BIOLOGYT32GM007270 · NIGMS · UNIVERSITY OF WASHINGTON · PI RAIBLE, DAVID W · 1985 to 2020
$21.0MT32 Predoctoral training grant in geneticsT32GM007103 · NIGMS · UNIVERSITY OF GEORGIA (UGA) · PI DYER, KELLY A · 1985 to 2021
$5.9MThe role of intestinal microbiota in graft-versus-host diseaseR01CA228308 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Philip L Lorenzi, Marcel R M van den Brink · 2018 to 2026
$5.2MThe role of autophagy gene Atg16L1 in allogeneic hematopoietic stem cell transplantation - Resubmission - 1R01HL123340 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CADWELL, KEN HASHIGIWA, VAN DEN BRINK, MARCEL R M · 2015 to 2022
$5.2MPromoting T cell reconstitution after hematopoietic cell transplantationR35HL171556 · NHLBI · FRED HUTCHINSON CANCER CENTER · PI Jarrod Dudakov · 2024 to 2026
$3.6MModulation of signaling from damage-associated molecular patterns to improve radiation-induced thymic dysfunctionU01AI170035 · NIAID · FRED HUTCHINSON CANCER CENTER · PI Jarrod Dudakov · 2022 to 2026
$3.0MHarnessing endogenous mechanisms of thymic regeneration toboost immune function in recipients of hematopoietic cell transplantR01HL145276 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI DUDAKOV, JARROD · 2019 to 2023
$2.8MThird-party “off the shelf” mature or precursor CAR T cells to prevent or treat malignant relapse after allo HCTR01HL147584 · NHLBI · SLOAN-KETTERING INST CAN RESEARCH · PI VAN DEN BRINK, MARCEL R M · 2019 to 2022
$2.7MCancer Council Victoria 1102104Cancer Council Victoria 1146518Department of Health | National Health and Medical Research Council (NHMRC) 1078763Department of Health | National Health and Medical Research Council (NHMRC) 1090236Department of Health | National Health and Medical Research Council (NHMRC) 1121325Department of Health | National Health and Medical Research Council (NHMRC) 1158024Department of Health | National Health and Medical Research Council (NHMRC) 1187367European Molecular Biology Organization (EMBO) ALTF-431-2017NCI NIH HHS K08 CA293271NCI NIH HHS P01 CA023766NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA015704NCI NIH HHS R01 CA228308NCI NIH HHS R01 CA228358NHLBI NIH HHS F30 HL165761NHLBI NIH HHS R01 HL123340NHLBI NIH HHS R01 HL145276NHLBI NIH HHS R01 HL147584NHLBI NIH HHS R01 HL165673NHLBI NIH HHS R35 HL171556NIAID NIH HHS U01 AI170035NIA NIH HHS P01 AG052359NIGMS NIH HHS T32 GM007103NIGMS NIH HHS T32 GM007270U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P30-CA015704U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01-CA228308U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) F30-HL165761U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01-HL123340U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01-HL145276U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01-HL147584U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01-HL165673U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R35-HL-171556U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) U01-AI70035U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) T32-GM007270U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) P01-AG052359
Abstract
The thymus is essential for establishing adaptive immunity yet undergoes age-related involution that leads to compromised immune responsiveness. The thymus is also extremely sensitive to acute insult and although capable of regeneration, this capacity declines with age for unknown reasons. We applied single-cell and spatial transcriptomics, lineage-tracing and advanced imaging to define age-related changes in nonhematopoietic stromal cells and discovered the emergence of two atypical thymic epithelial cell (TEC) states. These age-associated TECs (aaTECs) formed high-density peri-medullary epithelial clusters that were devoid of thymocytes; an accretion of nonproductive thymic tissue that worsened with age, exhibited features of epithelial-to-mesenchymal transition and was associated with downregulation of FOXN1. Interaction analysis revealed that the emergence of aaTECs drew tonic signals from other functional TEC populations at baseline acting as a sink for TEC growth factors. Following acute injury, aaTECs expanded substantially, further perturbing trophic regeneration pathways and correlating with defective repair of the involuted thymus. These findings therefore define a unique feature of thymic involution linked to immune aging and could have implications for developing immune-boosting therapies in older individuals.
Indexed as
AgingEpithelial CellsForkhead Transcription FactorsRegenerationThymus GlandAnimalsEpithelial-Mesenchymal TransitionFemaleMaleMiceMice, Inbred C57BLSingle-Cell AnalysisThymocytesForkhead Transcription FactorsWhn protein
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