ArticleScientific reports2021
BCG therapy is associated with long-term, durable induction of Treg signature genes by epigenetic modulation.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Multiple BCG vaccinations for the prevention of COVID-19 and other infectious diseases in type 1 diabetes.Cell reports. Medicine · 2022Trial
- Review
- Long-Term Impact of Historical BCG Vaccination Policies on Parkinson's Disease Risk: A Hypothesis-Generating Retrospective Cohort Analysis.Biomedicines · 2026Article
- Bacillus Calmette-Guérin (BCG) immunotherapy reprograms CNS immunity and alters Alzheimer's biomarkers: results from two open-label clinical trials.Communications medicine · 2026Article
- Malathion-induced neurological alterations associated with dysregulation of RORγt/STAT3/IL-17 and FOXP3/STAT5/IL-10 pathways: potential neuroprotective effects of BCG.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- BCG Impact on PD-1/PD-L1 Expression in Peripheral Immunocytes of Cancer Patients-A Potential Explanation for Its Activity in Preventing Alzheimer's Disease.Current issues in molecular biology · 2025Article
- Recombinant BCG Expressing IL-12 as A Novel Immunomodulatory Strategy for Allergic Asthma: Opportunities and Challenges.Clinical reviews in allergy & immunology · 2025Review
- From Bench to Bladder: The Rise in Immune Checkpoint Inhibition in the Treatment of Non-Muscle Invasive Bladder Cancer.Cancers · 2025Review
- Tuberculosis in patients with systemic lupus erythematosus.Frontiers in immunology · 2025Review
- Bacillus Calmette-Guérin (BCG)-Induced Protection in Brain Disorders.Inflammation · 2024Review
- Late in the US pandemic, multi-dose BCG vaccines protect against COVID-19 and infectious diseases.iScience · 2024Article
- BCG Vaccination Suppresses Glucose Intolerance Progression in High-Fat-Diet-Fed C57BL/6 Mice.Medicina (Kaunas, Lithuania) · 2024Article
- Article
- Reduction of hyperglycemia in STZ-induced diabetic mice by prophylactic treatment with heat-killedFrontiers in endocrinology · 2024Article
- Association of BCG Vaccine Treatment With Death and Dementia in Patients With Non-Muscle-Invasive Bladder Cancer.JAMA network open · 2023Article
- BCG Vaccination and the Risk of Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis.Pathogens (Basel, Switzerland) · 2023Review
- Glucose metabolism and its role in the maturation and migration of human CD1cFrontiers in cellular and infection microbiology · 2023Article
- Advances in computational frameworks in the fight against TB: The way forward.Frontiers in pharmacology · 2023Review
- Research progress on specific and non-specific immune effects of BCG and the possibility of BCG protection against COVID-19.Frontiers in immunology · 2023Review
- Immunogenicity and efficacy of an oral live-attenuated vaccine for bovine Johne's disease.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Induction of immunosuppressive T-regulatory cells (Tregs) is a desirable goal in autoimmunity, and perhaps other immune diseases of activation. One promising avenue is with the bacille-calmette-guérin (BCG) vaccine in autoimmune type 1 diabetes (T1D). Its administration is associated with gradual clinical improvements in human autoimmunity over a 2-3 year post-vaccination period. We hypothesize that those improvements, and their unusually long time course to fully materialize, are partially attributable to BCG's induction of Tregs. Here we report on a 3 year-long longitudinal cohort of T1Ds and examine the mechanism by which Treg induction occurs. Using the Human Infinium Methylation EPIC Bead Chip, we show that BCG vaccination is associated with gradual demethylation of most of 11 signature genes expressed in highly potent Tregs: Foxp3, TNFRSF18, CD25, IKZF2, IKZF4, CTLA4, TNFR2, CD62L, Fas, CD45 and IL2; nine of these 11 genes, by year 3, became demethylated at the majority of CpG sites. The Foxp3 gene was studied in depth. At baseline Foxp3 was over-methylated compared to non-diabetic controls; 3 years after introduction of BCG, 17 of the Foxp3 gene's 22 CpG sites became significantly demethylated including the critical TSDR region. Corresponding mRNA, Treg expansion and clinical improvement supported the significance of the epigenetic DNA changes. Taken together, the findings suggest that BCG has systemic impact on the T cells of the adaptive immune system, and restores immune balance through Treg induction.
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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.