Regulatory Multitasking of Tolerogenic Dendritic Cells – Lessons Taken from Vitamin D3-Treated Tolerogenic Dendritic Cells
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Tolerogenic dendritic cells (DCs) work through silencing of differentiated antigen-specific T cells, activation and expansion of naturally occurring T regulatory cells (Tregs), transfer of regulatory properties to T cells, and the differentiation of naïve T cells into Tregs. Due to an operational definition based on T cell activation assays, the identity of tolerogenic DCs has been a matter of debate and it need not represent a specialized DC subset. Human tolerogenic DCs generated in vitro using inhibitory cytokines, growth factors, natural immunomodulators, or genetic manipulation have been effective and several of these tolerogenic DCs are currently being tested for clinical use. Ex vivo generated tolerogenic DCs reduce activation of naïve T cells using various means, promote a variety of regulatory T cells and most importantly, frequently show stable inhibitory phenotypes upon repetitive maturation with inflammatory factors. Yet, tolerogenic DCs differ with respect to the phenotype or the number of regulatory mechanisms they employ to modulate the immune system. In our experience, tolerogenic DCs generated using the biologically active form of vitamin D (VD3-DCs), alone, or combined with dexamethasone are proficient in their immunoregulatory functions. These tolerogenic DCs show a stable maturation-resistant semi-mature phenotype with low expression of activating co-stimulatory molecules, no production of the IL-12 family of cytokines and high expression of inhibitory molecules and IL-10. VD3-DCs induce increased apoptosis of effector T cells and induce antigen-specific regulatory T cells, which work through linked suppression ensuring infectious tolerance. Lessons learned on VD3-DCs help understanding the contribution of different pattern-recognition receptors (PRRs) and secondary signals to the tolerogenic function and how a cross-talk between DCs and T cells translates into immune regulation.
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Vitamin D is an important factor in the development of tolerogenic dendritic cells and T regulatory lymphocytes.
“Vitamin D is an important factor in the development of tolerogenic dendritic cells and T regulatory lymphocytes [101].”
From Interaction of the endocrine system with inflammation: a function of energy and volume regulation (2014) · cites this paper as [101]
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Sorted by citations
Mechanisms in endocrinology: vitamin D as a potential contributor in endocrine health and disease
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Interaction of the endocrine system with inflammation: a function of energy and volume regulation
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“Vitamin D is an important factor in the development of tolerogenic dendritic cells and T regulatory lymphocytes [101].”
Background
- Authors
- Nikolic, T., & Roep, B. O.
- Affiliations
- Leiden University Medical Center (NL)
- Corresponding author
- Roep, Bart O.
- ORCID
- Roep, Bart O.
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2013
- Volume
- 4
- Pages
- 113-113
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC3653108
- OpenAlex
- W2013395898
- Cited by
- 112
- References
- 126
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 9 · 2022: 5 · 2021: 10 · 2020: 14 · 2019: 7 · 2018: 14 · 2017: 12 · 2016: 9 · 2015: 8 · 2014: 9 · 2013: 7
- FWCI
- 6.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- tolerogenic dendritic cells, vitamin D3, dexamethasone, regulatory T cells, immune regulation, DC maturation, IL-10, pattern recognition receptors, T cell apoptosis, infectious tolerance, ex vivo dendritic cell generation
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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