ArticleProceedings of the National Academy of Sciences of the United States of America2015
Selective NFAT targeting in T cells ameliorates GvHD while maintaining antitumor activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 46 citations in OpenAlex.
- Allogeneic haematopoietic cell transplantation promotes atherosclerosis in mice via CD8+ T cells.Cardiovascular research · 2025Article
- NFAT single-deficient murine T cells reduce the risk of aGvHD while controlling cytomegalovirus infection.iScience · 2025Article
- Oligoclonal CD4Communications biology · 2024Article
- NFAT signaling is indispensable for persistent memory responses of MCMV-specific CD8+ T cells.PLoS pathogens · 2024Article
- Galectin-3 expression in donor T cells reduces GvHD severity and lethality after allogeneic hematopoietic cell transplantation.Cell reports · 2023Article
- Dissecting the regulatory network of transcription factors in T cell phenotype/functioning during GVHD and GVT.Frontiers in immunology · 2023Review
- Dual JAK2/Aurora kinase A inhibition prevents human skin graft rejection by allo-inactivation and ILC2-mediated tissue repair.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022Article
- Article
- Calcineurin inhibitors target Lck activation in graft-versus-host disease.The Journal of clinical investigation · 2021Article
- Lack of NFATc1 SUMOylation prevents autoimmunity and alloreactivity.The Journal of experimental medicine · 2021Article
- NFATc1/αA and Blimp-1 Support the Follicular and Effector Phenotype of Tregs.Frontiers in immunology · 2021Article
- T-Cell Metabolism in GraftFrontiers in immunology · 2021Review
- T Helper Cell Lineage-Defining Transcription Factors: Potent Targets for Specific GVHD Therapy?Frontiers in immunology · 2021Review
- Rapid and Efficient Gene Editing for Direct Transplantation of Naive Murine Cas9Frontiers in immunology · 2021Article
- Roles of IL-2 in bridging adaptive and innate immunity, and as a tool for cellular immunotherapy.Journal of leukocyte biology · 2020Review
- Urethral meatus stricture BOO stimulates bladder smooth muscle cell proliferation and pyroptosis via IL‑1β and the SGK1‑NFAT2 signaling pathway.Molecular medicine reports · 2020Article
- Article
- Metabolic reprogramming augments potency of human pSTAT3-inhibited iTregs to suppress alloreactivity.JCI insight · 2020Article
- Calcineurin inhibitors reduce NFAT-dependent expression of antifungal pentraxin-3 by human monocytes.Journal of leukocyte biology · 2020Article
- Targeting Interleukin-2-Inducible T-Cell Kinase (ITK) Differentiates GVL and GVHD in Allo-HSCT.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Graft-versus-host disease (GvHD) is a life-threatening immunological complication after allogenic hematopoietic stem cell transplantation (allo-HCT). The intrinsic graft-versus-leukemia (GvL) effect, however, is the desirable curative benefit. Patients with acute GvHD are treated with cyclosporine A (CsA) or tacrolimus (FK506), which not only often causes severe adverse effects, but also interferes with the anticipated GvL. Both drugs inhibit calcineurin, thus at first suppressing activation of the nuclear factor of activated T cells (NFAT). Therefore, we explored the specific contribution of individual NFAT factors in donor T cells in animal models of GvHD and GvL. Ablation of NFAT1, NFAT2, or a combination of both resulted in ameliorated GvHD, due to reduced proliferation, target tissue homing, and impaired effector function of allogenic donor T cells. In contrast, the frequency of Foxp3(+) regulatory T (Treg) cells was increased and NFAT-deficient Tregs were fully protective in GvHD. CD8(+) T-cell recall response and, importantly, the beneficial antitumor activity were largely preserved in NFAT-deficient effector T cells. Thus, specific inhibition of NFAT opens an avenue for an advanced therapy of GvHD maintaining protective GvL.
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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.