ArticleScience immunology2018
Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration.
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Article in Science immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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99citing papers in PubMed
5.4field-weighted citation impact, top 3% of its field
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Who cites it
99 citing papers in PubMed, 131 citations in OpenAlex.
- Mesenchymal thymic niche cells enable regeneration of the adult thymus and T cell immunity.Nature biotechnology · 2026Article
- Rag1-based time-stamp tracing of T-cell developmental origins.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Clinical rationale for thymic restoration in adult immunosenescence.Immunity & ageing : I & A · 2026Review
- Fibroblast-driven collagen expansion and altered thymic medullary niches in 22q11.2 deletion syndrome.Journal of human immunity · 2026Article
- Thymus and Leishmania at the Crossroads: Autoimmunity and Cancer.Immunology · 2026Review
- From Development to Aging: Dynamic Roles of the Thymic Medulla in T Cell Biology.Immunological reviews · 2026Review
- Thymus engraftment and developmental progression of adoptively transferred progenitor T cells are affected by host conditioning.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Morphometric analysis of the thymic epithelial cell network using integrated and orthogonal digital pathology approaches.Communications biology · 2026Article
- Proteasome inhibition promotes Foxn1 expression in thymic epithelial cells and induces thymic regeneration in mice.Cell death and differentiation · 2026Article
- Damage-induced pyroptosis drives endogenous thymic regeneration by activating the purinergic receptor P2Y2.Cell death & disease · 2026Article
- Identifying space-resolved proteins of the murine thymus, by combining MALDI-MSI and proteomics.Life science alliance · 2026Article
- Hyperoxia promotes bronchopulmonary dysplasia via Noggin-mediated BMP4 antagonism and cellular senescence.Frontiers in physiology · 2026Article
- Radioresistant intrathymic stem cells: retrospective analysis and concept of the role in thymic oncogenesis and post-irradiation regeneration.Frontiers in immunology · 2026Review
- Thymic regeneration and tumor immunotherapy.Frontiers in immunology · 2026Review
- Network-orchestrated regulation of thymic dysfunction and restoration.Frontiers in immunology · 2026Review
- Damage-induced IL-18 stimulates thymic NK cells limiting endogenous tissue regeneration.Nature immunology · 2025Article
- Cytoskeleton proteins, the structural basis of T-lymphocyte and TEC restructure during rapid thymus regeneration.Histology and histopathology · 2025Review
- Burning Down the House: Thymic Repair and Regeneration After Acute Damage.Immunological reviews · 2025Review
- It's Time to Unite: Diversity and Coordination of Thymic Stromal Cells for T Cell Selection and Organ Integrity.Immunological reviews · 2025Review
- Endogenous thymic regeneration: restoring T cell production following injury.Nature reviews. Immunology · 2025Review
39 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 7 institutions in 2 countries.
Tobias WertheimerImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.ORCID 0000-0002-8480-7391
Enrico VelardiImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.ORCID 0000-0001-8383-0453
Jennifer TsaiImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.ORCID 0000-0002-9267-4584
Kirsten CooperProgram in Immunology, Clinical Research Division, and Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.ORCID 0000-0002-0711-2713
Shiyun XiaoDepartment of Genetics, University of Georgia, Athens, GA 30602, USA.ORCID 0000-0003-0196-287X
Christopher C KlossDepartment of Genetic Medicine and Ansary Stem Cell Institute, Weill Cornell Medical College, New York, NY 10021, USA.ORCID 0000-0002-5212-2216
Katja J OttmüllerDepartment of Medicine II, Würzburg University Hospital, Interdisciplinary Center for Clinical Research (IZKF), and Graduate School of Life Sciences, University of Würzburg, Würzburg, Germany.ORCID 0000-0001-5162-7266
Zeinab MokhtariDepartment of Medicine II, Würzburg University Hospital, Interdisciplinary Center for Clinical Research (IZKF), and Graduate School of Life Sciences, University of Würzburg, Würzburg, Germany.
Christian BredeDepartment of Medicine II, Würzburg University Hospital, Interdisciplinary Center for Clinical Research (IZKF), and Graduate School of Life Sciences, University of Würzburg, Würzburg, Germany.
Paul deRoosProgram in Immunology, Clinical Research Division, and Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Sinéad KinsellaProgram in Immunology, Clinical Research Division, and Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Brisa PalikuqiDepartment of Genetic Medicine and Ansary Stem Cell Institute, Weill Cornell Medical College, New York, NY 10021, USA.ORCID 0000-0003-3164-3626
Michael GinsbergAngiocrine Bioscience, San Diego, CA 92130, USA.
Lauren F YoungImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.ORCID 0000-0003-2220-0508
Fabiana KreinesImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.ORCID 0000-0001-6745-1998
Sophia R LiebermanImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Amina LazrakImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Peipei GuoDepartment of Genetic Medicine and Ansary Stem Cell Institute, Weill Cornell Medical College, New York, NY 10021, USA.
Florent MalardImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.ORCID 0000-0002-3474-0002
Odette M SmithImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Yusuke ShonoImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.ORCID 0000-0002-0459-1659
Robert R JenqDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.ORCID 0000-0002-5434-439X
Alan M HanashDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.ORCID 0000-0002-3273-3634
Daniel J NolanAngiocrine Bioscience, San Diego, CA 92130, USA.ORCID 0000-0002-4913-0813
Jason M ButlerDepartment of Genetic Medicine and Ansary Stem Cell Institute, Weill Cornell Medical College, New York, NY 10021, USA.
Andreas BeilhackDepartment of Medicine II, Würzburg University Hospital, Interdisciplinary Center for Clinical Research (IZKF), and Graduate School of Life Sciences, University of Würzburg, Würzburg, Germany.ORCID 0000-0002-3165-2648
Nancy R ManleyDepartment of Genetics, University of Georgia, Athens, GA 30602, USA.
Shahin RafiiDepartment of Genetic Medicine and Ansary Stem Cell Institute, Weill Cornell Medical College, New York, NY 10021, USA.
Jarrod A DudakovProgram in Immunology, Clinical Research Division, and Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. jdudakov@fredhutch.org vandenbm@mskcc.org.ORCID 0000-0001-6220-5632
Marcel R M van den BrinkImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. jdudakov@fredhutch.org vandenbm@mskcc.org.ORCID 0000-0003-0696-4401
Memorial Sloan Kettering Cancer Center · USCornell University · USUniversitätsklinikum Würzburg · DEFred Hutch Cancer Center · USAngiocrine Bioscience (United States) · USUniversity of Georgia · USUniversity of Washington · US
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
$23.5MStrategies to enhance immune reconstitution after bone marrow transplantR01HL069929 · NHLBI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI VAN DEN BRINK, MARCEL R M · 2002 to 2015
$7.0MThe role of intestinal microbiota in graft-versus-host diseaseR01CA228358 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI VAN DEN BRINK, MARCEL R M · 2018 to 2022
$2.6MStrategies to Enhance Lymphoid Recovery After Radiation-Induced InjuryR01AI080455 · NIAID · SLOAN-KETTERING INST CAN RESEARCH · PI VAN DEN BRINK, MARCEL R M · 2008 to 2012
$2.6MIL-22 in Thymic RegenerationR01AI101406 · NIAID · SLOAN-KETTERING INST CAN RESEARCH · PI VAN DEN BRINK, MARCEL R M · 2012 to 2016
$2.5MMucosal Immunity and Microbiota in Intestinal Graft-versus-Host DiseaseR01AI100288 · NIAID · SLOAN-KETTERING INST CAN RESEARCH · PI VAN DEN BRINK, MARCEL R M · 2012 to 2016
$2.2MInvestigating the role of interleukin-22 in thymus functionR00CA176376 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI DUDAKOV, JARROD · 2016 to 2018
$741kIL-22 in epithelial regeneration after allogeneic transplantK08HL115355 · NHLBI · SLOAN-KETTERING INST CAN RESEARCH · PI HANASH, ALAN M · 2012 to 2016
$719kNCI NIH HHS P01 CA023766NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA015704NCI NIH HHS R00 CA176376NCI NIH HHS R01 CA228358NHLBI NIH HHS K08 HL115355NHLBI NIH HHS R01 HL069929NIAID NIH HHS R01 AI080455NIAID NIH HHS R01 AI100288NIAID NIH HHS R01 AI101406NIA NIH HHS P01 AG052359
Abstract
The thymus is not only extremely sensitive to damage but also has a remarkable ability to repair itself. However, the mechanisms underlying this endogenous regeneration remain poorly understood, and this capacity diminishes considerably with age. We show that thymic endothelial cells (ECs) comprise a critical pathway of regeneration via their production of bone morphogenetic protein 4 (BMP4) ECs increased their production of BMP4 after thymic damage, and abrogating BMP4 signaling or production by either pharmacologic or genetic inhibition impaired thymic repair. EC-derived BMP4 acted on thymic epithelial cells (TECs) to increase their expression of
Indexed as
AnimalsBone Morphogenetic Protein 4Cell ProliferationEndothelial CellsEpithelial CellsFemaleForkhead Transcription FactorsMiceMice, Inbred C57BLRegenerationSignal TransductionStem CellsThymus GlandT-LymphocytesBmp4 protein, mouseBone Morphogenetic Protein 4Forkhead Transcription Factors
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