ArticlePloS one2015
Targeting Tuberculosis and HIV Infection-Specific Regulatory T Cells with MEK/ERK Signaling Pathway Inhibitors.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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
17 citing papers in PubMed, 25 citations in OpenAlex.
- Antiviral and immunomodulatory effect of zapnometinib in animal models and hospitalized COVID-19 patients.Frontiers in immunology · 2025Trial
- High-Throughput Phenotypic Screen to Identify FoxP3 Regulators in Primary T Cells.ACS chemical biology · 2026Article
- MAPK signaling pathways in host immune regulation during Mycobacterium tuberculosis infection.Frontiers in immunology · 2026Review
- Dysregulation of the JNK signaling pathway in tuberculosis: mechanisms and therapeutic strategies.Frontiers in cellular and infection microbiology · 2025Review
- Repurposing Anticancer Drugs Targeting the MAPK/ERK Signaling Pathway for the Treatment of Respiratory Virus Infections.International journal of molecular sciences · 2024Review
- MEK-inhibitor treatment reduces the induction of regulatory T cells in mice after influenza A virus infection.Frontiers in immunology · 2024Article
- The antiviral effects of a MEK1/2 inhibitor promote tumor regression in a preclinical model of human papillomavirus infection-induced tumorigenesis.Antiviral research · 2023Article
- Proteomics and Phosphoproteomic Analysis to Identify Spleen of Takifugu rubripes Infected Cryptocaryon irritans.Marine biotechnology (New York, N.Y.) · 2023Article
- MEK inhibitors as novel host-targeted antivirals with a dual-benefit mode of action against hyperinflammatory respiratory viral diseases.Current opinion in virology · 2023Review
- Corticosteroid-Refractory Myositis After Dual BRAF and MEK Inhibition in a Patient with BRAF V600E-Mutant Metastatic Intrahepatic Cholangiocarcinoma.Journal of immunotherapy and precision oncology · 2022Article
- Pharmacokinetics, Pharmacodynamics and Antiviral Efficacy of the MEK Inhibitor Zapnometinib in Animal Models and in Humans.Frontiers in pharmacology · 2022Article
- Pharmacokinetics, absorption, distribution, metabolism and excretion of the MEK inhibitor zapnometinib in rats.Frontiers in pharmacology · 2022Article
- Neuromuscular Complications of Targeted Anticancer Agents: Can Tyrosine Kinase Inhibitors Induce Myasthenia Gravis? Getting Answers From a Case Report up to a Systematic Review.Frontiers in oncology · 2021Article
- CKS1B as Drug Resistance-Inducing Gene-A Potential Target to Improve Cancer Therapy.Frontiers in oncology · 2020Review
- Downregulation of CKS1B restrains the proliferation, migration, invasion and angiogenesis of retinoblastoma cells through the MEK/ERK signaling pathway.International journal of molecular medicine · 2019Article
- Immunometabolism and Pulmonary Infections: Implications for Protective Immune Responses and Host-Directed Therapies.Frontiers in microbiology · 2019Review
- Adjunct Strategies for Tuberculosis Vaccines: Modulating Key Immune Cell Regulatory Mechanisms to Potentiate Vaccination.Frontiers in immunology · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human regulatory T cells (Tregs) are essential in maintaining immunological tolerance and suppress effector T cells. Tregs are commonly up-regulated in chronic infectious diseases such as tuberculosis (TB) and human immunodeficiency virus (HIV) infection and thereby hamper disease-specific immune responses and eradication of pathogens. The MEK/ERK signaling pathway is involved in regulation of the FoxP3 transcription factor, which directs a lineage-specific transcriptional program to define Tregs and control their suppressive function. Here, we aimed to target activation of disease-specific Tregs by inhibition of the MEK/ERK signaling pathway based on the hypothesis that this would improve anti-HIV and anti-TB immunity. Stimulation of T cells from untreated TB (n = 12) and HIV (n = 8) patients with disease-specific antigens in vitro in the presence of the MEK inhibitor (MEKI) trametinib (GSK1120212) resulted in significant down-regulation of both FoxP3 levels (MFI) and fractions of resting (CD45RA+FoxP3+) and activated (CD45RA-FoxP3++) Tregs. MEKI also reduced the levels of specific T effector cells expressing the pro-inflammatory cytokines (IFN-γ, TNF-α and IL-2) in both HIV and TB patients. In conclusion, MEKIs modulate disease antigen-specific Treg activation and may have potential application in new treatment strategies in chronic infectious diseases where reduction of Treg activity would be favorable. Whether MEKIs can be used in current HIV or TB therapy regimens needs to be further investigated.
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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.