ArticleBlood2015
Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response including LAP+CD4+ T cells.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 59 citations in OpenAlex.
- AAV Gene Therapy for MPS IVA with Induction of Immune Tolerance via Oral Administration of Epitope Peptides of N-Acetylgalactosamine-6-sulfate Sulfatase.International journal of molecular sciences · 2026Article
- The use of Bacillus subtilis as a cost-effective expression system for production of Cholera Toxin B fused factor VIII epitope regions applicable for inducing oral immune tolerance.Folia microbiologica · 2024Article
- Factor IX administration in the skin primes inhibitor formation and sensitizes hemophilia B mice to systemic factor IX administration.Research and practice in thrombosis and haemostasis · 2023Article
- Suppression of anti-drug antibody formation against coagulation factor VIII by oral delivery of anti-CD3 monoclonal antibody in hemophilia A mice.Cellular immunology · 2023Article
- Distinct functions and transcriptional signatures in orally induced regulatory T cell populations.Frontiers in immunology · 2023Article
- Oral tolerance to prevent anti-drug antibody formation in protein replacement therapies.Cellular immunology · 2022Review
- Lactoferrin Alleviates Lipopolysaccharide-Induced Infantile Intestinal Immune Barrier Damage by Regulating an ELAVL1-Related Signaling Pathway.International journal of molecular sciences · 2022Article
- Article
- LAP+CD4+T cells regulate the anti-tumor role of CIK cells in colorectal cancer through IL-10 and TGF-β.American journal of translational research · 2022Article
- Preclinical development of plant-based oral immune modulatory therapy for haemophilia B.Plant biotechnology journal · 2021Article
- Cas9-directed immune tolerance in humans-a model to evaluate regulatory T cells in gene therapy?Gene therapy · 2021Review
- Oral delivery of therapeutic proteins bioencapsulated in plant cells: preclinical and clinical advances.Current opinion in colloid & interface science · 2021Article
- Role of orally induced regulatory T cells in immunotherapy and tolerance.Cellular immunology · 2021Review
- Oral delivery of novel human IGF-1 bioencapsulated in lettuce cells promotes musculoskeletal cell proliferation, differentiation and diabetic fracture healing.Biomaterials · 2020Article
- Factor VIII: Perspectives on Immunogenicity and Tolerogenic Strategies for Hemophilia A Patients.International journal of molecular and cellular medicine · 2020Review
- Role of Small Intestine and Gut Microbiome in Plant-Based Oral Tolerance for Hemophilia.Frontiers in immunology · 2020Article
- Plant cell-made protein antigens for induction of Oral tolerance.Biotechnology advances · 2019Review
- Complexity of immune responses to AAV transgene products - Example of factor IX.Cellular immunology · 2019Review
- Reprogrammed CD4Frontiers in immunology · 2019Article
- Tolerance induction in hemophilia: innovation and accomplishments.Current opinion in hematology · 2018Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Coagulation factor replacement therapy for the X-linked bleeding disorder hemophilia is severely complicated by antibody ("inhibitor") formation. We previously found that oral delivery to hemophilic mice of cholera toxin B subunit-coagulation factor fusion proteins expressed in chloroplasts of transgenic plants suppressed inhibitor formation directed against factors VIII and IX and anaphylaxis against factor IX (FIX). This observation and the relatively high concentration of antigen in the chloroplasts prompted us to evaluate the underlying tolerance mechanisms. The combination of oral delivery of bioencapsulated FIX and intravenous replacement therapy induced a complex, interleukin-10 (IL-10)-dependent, antigen-specific systemic immune suppression of pathogenic antibody formation (immunoglobulin [Ig] 1/inhibitors, IgE) in hemophilia B mice. Tolerance induction was also successful in preimmune mice but required prolonged oral delivery once replacement therapy was resumed. Orally delivered antigen, initially targeted to epithelial cells, was taken up by dendritic cells throughout the small intestine and additionally by F4/80(+) cells in the duodenum. Consistent with the immunomodulatory responses, frequencies of tolerogenic CD103(+) and plasmacytoid dendritic cells were increased. Ultimately, latency-associated peptide expressing CD4(+) regulatory T cells (CD4(+)CD25(-)LAP(+) cells with upregulated IL-10 and transforming growth factor-β (TGF-β) expression) as well as conventional CD4(+)CD25(+) regulatory T cells systemically suppressed anti-FIX responses.
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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.