ArticleCytometry. Part A : the journal of the International Society for Analytical Cytology2013
Nuclear translocation of nuclear factor of activated T cells (NFAT) as a quantitative pharmacodynamic parameter for tacrolimus.
Article in Cytometry. Part A : the journal of the International Society for Analytical Cytology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Analysis of NFATc1 amplification in T cells for pharmacodynamic monitoring of tacrolimus in kidney transplant recipients.PloS one · 2018Trial
- Differential T Cell Signaling Pathway Activation by Tacrolimus and Belatacept after Kidney Transplantation: Post Hoc Analysis of a Randomised-Controlled Trial.Scientific reports · 2017Trial
- Bioelectric warfare on bone infection: The role of piezoelectric biomaterials in osteomyelitis management.Fundamental research · 2026Review
- Post-transplant hepatocellular carcinoma: balancing immunosuppression and immune checkpoint inhibitors.Clinical and molecular hepatology · 2026Review
- TRPM7 and magnesium orchestrate human CD4 T-cell activation and differentiation.Life science alliance · 2026Article
- Breaking the barrier: oral tacrolimus plus apremilast rescues acute generalized pustular psoriasis with severe comorbidities-a case report.Frontiers in immunology · 2026Article
- Engineering human Tregs to resist tacrolimus via FKBP12 gene editing.Frontiers in immunology · 2026Article
- Exploring the tumor microenvironment of colorectal cancer patients post renal transplantation by single-cell analysis.Cancer science · 2025Article
- Challenges and future perspectives for high-throughput chimeric antigen receptor T cell discovery.Current opinion in biotechnology · 2024Review
- Article
- Toward high-throughput engineering techniques for improving CAR intracellular signaling domains.Frontiers in bioengineering and biotechnology · 2023Article
- Maintenance Immunosuppression in Solid Organ Transplantation: Integrating Novel Pharmacodynamic Biomarkers to Inform Calcineurin Inhibitor Dose Selection.Clinical pharmacokinetics · 2020Review
- A 3D culture platform enables development of zinc-binding prodrugs for targeted proliferation of β cells.Science advances · 2020Article
- Calcium inhibitor inhibits high glucose‑induced hypertrophy of H9C2 cells.Molecular medicine reports · 2020Article
- Tacrolimus increases the expression level of the chemokine receptor CXCR2 to promote renal fibrosis progression.International journal of molecular medicine · 2019Article
- Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition).European journal of immunology · 2019Article
- Article
- Chimeric Antigen Receptor Library Screening Using a Novel NF-κB/NFAT Reporter Cell Platform.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Total cellular protein presence of the transcription factor IRF8 does not necessarily correlate with its nuclear presence.Methods (San Diego, Calif.) · 2017Article
- Quantifying MHC dextramer-induced NFAT activation in antigen-specific T cells as a functional response parameter.Methods (San Diego, Calif.) · 2017Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Nuclear factor of activated T cells (NFAT) is a family of transcription factors involved in regulating the immune response. The canonical NFAT pathway is calcium-dependent and upon activation, NFAT is dephosphorylated by the phosphatase, calcineurin. This results in its translocation from the cytoplasm to the nucleus and transcription of downstream target genes that include the cytokines IL-2, IL-10, and IFNγ. Calcineurin inhibitors including tacrolimus inhibit the NFAT pathway and are used as immunosuppressants in transplant settings to prevent graft rejection. There is, as yet, no direct means to monitor tacrolimus pharmacodynamics. In this study, a rapid, quantitative, image cytometry-based measurement of nuclear translocation of NFAT1 is used to evaluate NFAT activation in T cells and its tacrolimus-induced inhibition. A strong dose-dependent correlation between NFAT1 inhibition and tacrolimus dose is demonstrated in vitro. Time kinetic analysis of NFAT1 inhibition in plasma from stable renal transplant recipients before and after an in vivo dose with tacrolimus correlated with the expected pharmacokinetic profile of tacrolimus. This was further corroborated by analysis of patients' autologous CD4 and CD8 T cells. This is the first report to show that the measurement of NFAT1 activation potential by nuclear translocation can be used as a direct, sensitive, reproducible and quantitative pharmacodynamic readout for tacrolimus action. These results, and the rapid turnaround time for this assay, warrant its evaluation in a larger clinical setting to assess its role in therapeutic drug monitoring of calcineurin inhibitors.
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