ArticleCancer biology & therapy2017
Vitamin D decreases STAT phosphorylation and inflammatory cytokine output in T-LGL leukemia.
Article in Cancer biology & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Trial
- Sterile inflammation in laminopathies.European journal of cell biology · 2025Review
- Tail Fin Regeneration in Zebrafish: The Role of Non-canonical Crosstalk Between STAT3 and Vitamin D Pathway.International journal of biological sciences · 2025Article
- Key genes of vitamin D metabolism and their roles in the risk and prognosis of cancer.Frontiers in genetics · 2025Review
- Review
- T-Cell Large Granular Lymphocytic Leukemia: A First Case Report Diagnosed by Flow Cytometry in Vietnam.Cureus · 2021Article
- Vitamin D protects glomerular mesangial cells from high glucose-induced injury by repressing JAK/STAT signaling.International urology and nephrology · 2021Article
- Therapeutic Effects of 25-Hydroxyvitamin D on the Pathological Process of Benign Prostatic Hyperplasia: An In Vitro Evidence.Disease markers · 2021Article
- JAK-STAT Inhibitors in Atopic Dermatitis from Pathogenesis to Clinical Trials Results.Microorganisms · 2020Review
- Vitamin D as a Primer for Oncolytic Viral Therapy in Colon Cancer Models.International journal of molecular sciences · 2020Article
- Large granular lymphocyte leukemia serum and corresponding hematological parameters reveal unique cytokine and sphingolipid biomarkers and associations with STAT3 mutations.Cancer medicine · 2020Article
- Observational
- 1α, 25 Dihydroxyvitamin D (1,25(OH)The Journal of steroid biochemistry and molecular biology · 2020Article
- IL-2 and IL-15 blockade by BNZ-1, an inhibitor of selective γ-chain cytokines, decreases leukemic T-cell viability.Leukemia · 2019Article
- Article
- Article
- Calcitriol-mediated reduction in IFN-γ output in T cell large granular lymphocytic leukemia requires vitamin D receptor upregulation.The Journal of steroid biochemistry and molecular biology · 2018Article
- [Vitamin D3 regulates mononuclear phagocyte polarization induced by serum from patients with ankylosing spondylitis].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2018Article
- Dysregulation of the IFN-γ-STAT1 signaling pathway in a cell line model of large granular lymphocyte leukemia.PloS one · 2018Article
- Vitamin D in hematological disorders and malignancies.European journal of haematology · 2017Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Large granular lymphocyte leukemia (LGLL) is a rare incurable chronic disease typically characterized by clonal expansion of CD3+ cytotoxic T-cells. Two signal transducer and activator of transcription factors, STAT1 and STAT3, are constitutively active in T-LGLL. Disruption of this activation induces apoptosis in T-LGLL cells. Therefore, considerable efforts are focused on developing treatments that inhibit STAT activation. Calcitriol, the active form of vitamin D, has been shown to decrease STAT1 and STAT3 phosphorylation in cancer cell lines and autoimmune disease mouse models. Thus, we investigated whether calcitriol could be a valid therapeutic for T-LGLL. Calcitriol treatment of the TL-1 cell line (model of T-LGLL) led to decreased phospho-Y701 STAT1 and phospho-Y705 STAT3 and increased vitamin D receptor (VDR) levels. Doses of 10 and 100 nM calcitriol also significantly decreased the inflammatory cytokine IFN-γ in the TL-1 cell line. The overall cell viability did not change when the TL-1 cell line was treated with 0.1 to 1000 nM calcitriol. Studies with primary T-LGLL patient peripheral blood mononuclear cells showed that the majority of T-LGLL patients have detectable VDR and activated STATs in contrast to normal donor controls. Treatment of primary T-LGLL patient cells with calcitriol recapitulated findings from the TL-1 cell line. Overall, our results suggest that calcitriol may reprogram T-cells to decrease essential STAT activation and pro-inflammatory cytokine output. These data support further investigation into calcitriol as an experimental therapeutic for T-LGLL.
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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.