ArticleBlood2022
Activation of the zinc-sensing receptor GPR39 promotes T-cell reconstitution after hematopoietic cell transplant in mice.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Zinc as a therapeutic adjunct: enhancing t-cell reconstitution in hematopoietic stem cell transplant recipients-a double-blind clinical study.BMC immunology · 2025Trial
- Isotopically enrichedScientific reports · 2026Article
- Immune reconstruction after allogeneic hematopoietic stem cell transplantation: rules, mechanisms, and applications.Annals of hematology · 2026Review
- Damage-induced pyroptosis drives endogenous thymic regeneration by activating the purinergic receptor P2Y2.Cell death & disease · 2026Article
- Zinc, type 2 diabetes, diabetic kidney disease: focus on hypoxia.Frontiers in endocrinology · 2026Review
- Damage-induced IL-18 stimulates thymic NK cells limiting endogenous tissue regeneration.Nature immunology · 2025Article
- ZIP10 as a potential therapeutic target in acute myeloid leukaemia.British journal of haematology · 2025Article
- Burning Down the House: Thymic Repair and Regeneration After Acute Damage.Immunological reviews · 2025Review
- Endogenous thymic regeneration: restoring T cell production following injury.Nature reviews. Immunology · 2025Review
- Thymic peptides in immune reconstitution and clinical outcome after allogeneic hematopoietic cell transplantation.Blood neoplasia · 2025Review
- Recirculating regulatory T cells mediate thymic regeneration through amphiregulin following damage.Immunity · 2025Article
- Hematopoietic stem cells: Understanding the mechanisms to unleash the therapeutic potential of hematopoietic stem cell transplantation.Stem cell research & therapy · 2025Review
- Hepatic zinc deficiency dampens the acute phase response in patients with alcohol-associated hepatitis.Frontiers in immunology · 2025Article
- Primary and secondary defects of the thymus.Immunological reviews · 2024Review
- Disorganization of secondary lymphoid organs and dyscoordination of chemokine secretion as key contributors to immune aging.Seminars in immunology · 2023Review
- Signaling pathway mechanisms of neurological diseases induced by G protein-coupled receptor 39.CNS neuroscience & therapeutics · 2023Review
- TC-G 1008 facilitates epileptogenesis by acting selectively at the GPR39 receptor but non-selectively activates CREB in the hippocampus of pentylenetetrazole-kindled mice.Cellular and molecular life sciences : CMLS · 2023Article
- Dietary regulation in health and disease.Signal transduction and targeted therapy · 2022Review
- Thymus, undernutrition, and infection: Approaching cellular and molecular interactions.Frontiers in nutrition · 2022Review
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Prolonged lymphopenia represents a major clinical problem after cytoreductive therapies such as chemotherapy and the conditioning required for hematopoietic stem cell transplant (HCT), contributing to the risk of infections and malignant relapse. Restoration of T-cell immunity depends on tissue regeneration in the thymus, the primary site of T-cell development, although the capacity of the thymus to repair itself diminishes over its lifespan. However, although boosting thymic function and T-cell reconstitution is of considerable clinical importance, there are currently no approved therapies for treating lymphopenia. Here we found that zinc (Zn) is critically important for both normal T-cell development and repair after acute damage. Accumulated Zn in thymocytes during development was released into the extracellular milieu after HCT conditioning, where it triggered regeneration by stimulating endothelial cell production of BMP4 via the cell surface receptor GPR39. Dietary supplementation of Zn was sufficient to promote thymic function in a mouse model of allogeneic HCT, including enhancing the number of recent thymic emigrants in circulation although direct targeting of GPR39 with a small molecule agonist enhanced thymic function without the need for prior Zn accumulation in thymocytes. Together, these findings not only define an important pathway underlying tissue regeneration but also offer an innovative preclinical approach to treat lymphopenia in HCT recipients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.