ArticleJournal of immunology (Baltimore, Md. : 1950)2014
All-trans retinoic acid induces arginase-1 and inducible nitric oxide synthase-producing dendritic cells with T cell inhibitory function.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Immune cells in liver transplantation: Dual roles, mechanistic insights, and targeted therapeutic strategies.Immunologic research · 2026Review
- Peptide hormones and bile acids shaping immune tolerance of the liver: implications and applications.Protein & cell · 2026Review
- Protocol of generation of tolerogenic dendritic cells affects their transcriptional and metabolic profiles leading to specific tolerogenic functions.Molecular therapy. Methods & clinical development · 2025Article
- Targeting Recipient Dendritic Cells with Sialic Acid-Modified Donor Alloantigen Prolongs Skin Transplant Survival.International journal of molecular sciences · 2025Article
- Enhancing plasmacytoid dendritic cell functionality withMolecular therapy. Oncology · 2025Article
- The pathogenic role of retinoid nuclear receptor signaling in cancer and metabolic syndromes.The Journal of experimental medicine · 2024Review
- NRF2 Plays a Crucial Role in the Tolerogenic Effect of Ethyl Pyruvate on Dendritic Cells.International journal of molecular sciences · 2024Article
- Dendritic Cells: A Bridge between Tolerance Induction and Cancer Development in Transplantation Setting.Biomedicines · 2024Review
- Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy.Journal of hematology & oncology · 2023Review
- WNT signaling in the tumor microenvironment promotes immunosuppression in murine pancreatic cancer.The Journal of experimental medicine · 2023Article
- Dendritic cells in liver transplantation immune response.Frontiers in cell and developmental biology · 2023Review
- The Effect of Arginase on Canine T-Lymphocyte Functions and its Modulation by All-Trans Retinoid Acid (ATRA) in Canine Monocyte-Derived Macrophages.Veterinary sciences · 2022Article
- Immunotherapy in soft tissue and bone sarcoma: unraveling the barriers to effectiveness.Theranostics · 2022Review
- Retinoic Acid-Containing Liposomes for the Induction of Antigen-Specific Regulatory T Cells as a Treatment for Autoimmune Diseases.Pharmaceutics · 2021Article
- Regulatory Macrophages and Tolerogenic Dendritic Cells in Myeloid Regulatory Cell-Based Therapies.International journal of molecular sciences · 2021Review
- All-trans retinoic acid overcomes solid tumor radioresistance by inducing inflammatory macrophages.Science immunology · 2021Article
- The Power of Plasticity-Metabolic Regulation of Hepatic Stellate Cells.Cell metabolism · 2021Review
- Lactoferrin Induces Tolerogenic Bone Marrow-Derived Dendritic Cells.Immune network · 2020Article
- Article
- Current Paradigms of Tolerogenic Dendritic Cells and Clinical Implications for Systemic Lupus Erythematosus.Cells · 2019Review
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Authors and funding
7 authors.
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Abstract
Hepatic stellate cells (HSC) are a major source of the immunoregulatory metabolite all-trans retinoic acid (ATRA), which may contribute to the generation of tolerogenic dendritic cells (DCs) in the liver. The present study seeks to clarify the mechanism(s) through which ATRA promotes the development of tolerogenic DCs. Although bone marrow-derived ATRA-treated DCs (RA-DCs) and conventional DCs had comparable surface phenotype, RA-DCs had diminished stimulatory capacity and could directly inhibit the expansion of DC/OVA-stimulated OT-II T cells. Arginase-1 (Arg-1) was found promote suppression because 1) ATRA was a potent inducer of Arg-1 protein and activity, 2) the Arg-1 inhibitor N(w)-hydroxy nor-l-arginine partially reversed suppression, and 3) the suppressive function of RA-DCs was partially compromised using OT-II T cells from GCN2(-/-) mice, which are insensitive to Arg-1. Inducible NO synthase (iNOS), however, was found to be a more significant contributor to RA-DC function because 1) ATRA potentiated the expression of IFN-γ-induced iNOS, 2) suppressive function in RA-DCs was blocked by the iNOS inhibitor N(G)-monomethyl-l-arginine, monoacetate salt, and 3) RA-DCs derived from iNOS(-/-) mice exhibited near complete loss of tolerogenic function, despite sustained Arg-1 activity. The expression of iNOS and the suppressive function of RA-DCs were dependent on both IFN-γ and ATRA. Furthermore, the in vivo behavior of RA-DCs proved to be consistent with their in vitro behavior. Thus, we conclude that ATRA enhances both Arg-1 and iNOS expression in IFN-γ-treated DCs, resulting in a tolerogenic phenotype. These findings elucidate mechanisms through which ATRA may contribute to liver immune tolerance.
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