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Tolerogenic dendrit...
Tolerogenic dendritic cells generated in vitro using a novel protocol mimicking mucosal tolerance mechanisms represent a potential therapeutic cell platform for induction of immune tolerance.
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- Dao Nyesiga, Gillian (author)
- Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces,Idogen AB, Lund, Sweden,Idogen AB, Sweden; Malmo Univ, Sweden
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- Pool, Lieneke (author)
- Idogen AB, Lund, Sweden
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- Englezou, Pavlos C (author)
- Idogen AB, Lund, Sweden
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- Hylander, Terese (author)
- Idogen AB, Lund, Sweden
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- Ohlsson, Lars (author)
- Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces,Malmo Univ, Sweden
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- Appelgren, Daniel (author)
- Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten
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- Sundstedt, Anette (author)
- Idogen AB, Lund, Sweden
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- Tillerkvist, Kristina (author)
- Idogen AB, Lund, Sweden
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- Romedahl, Hanne R (author)
- Idogen AB, Lund, Sweden
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- Wigren, Maria (author)
- Idogen AB, Lund, Sweden
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(creator_code:org_t)
- Frontiers Media S.A. 2023
- 2023
- English.
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In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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Abstract
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- Dendritic cells (DCs) are mediators between innate and adaptive immunity and vital in initiating and modulating antigen-specific immune responses. The most important site for induction of tolerance is the gut mucosa, where TGF-β, retinoic acid, and aryl hydrocarbon receptors collaborate in DCs to induce a tolerogenic phenotype. To mimic this, a novel combination of compounds – the synthetic aryl hydrocarbon receptor (AhR) agonist IGN-512 together with TGF-β and retinoic acid – was developed to create a platform technology for induction of tolerogenic DCs intended for treatment of several conditions caused by unwanted immune activation. These in vitro-generated cells, designated ItolDCs, are phenotypically characterized by their low expression of co-stimulatory and activating molecules along with high expression of tolerance-associated markers such as ILT3, CD103, and LAP, and a weak pro-inflammatory cytokine profile. When co-cultured with T cells and/or B cells, ItolDC-cultures contain higher frequencies of CD25+Foxp3+ regulatory T cells (Tregs), CD49b+LAG3+ ‘type 1 regulatory (Tr1) T cells, and IL-10-producing B cells and are less T cell stimulatory compared to cultures with matured DCs. Factor VIII (FVIII) and tetanus toxoid (TT) were used as model antigens to study ItolDC antigen-loading. ItolDCs can take up FVIII, process, and present FVIII peptides on HLA-DR. By loading both ItolDCs and mDCs with TT, antigen-specific T cell proliferation was observed. Cryo-preserved ItolDCs showed a stable tolerogenic phenotype that was maintained after stimulation with LPS, CD40L, or a pro-inflammatory cocktail. Moreover, exposure to other immune cells did not negatively impact ItolDCs’ expression of tolerogenic markers. In summary, a novel protocol was developed supporting the generation of a stable population of human DCs in vitro that exhibited a tolerogenic phenotype with an ability to increase proportions of induced regulatory T and B cells in mixed cultures. This protocol has the potential to constitute the base of a tolDC platform for inducing antigen-specific tolerance in disorders caused by undesired antigen-specific immune cell activation.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
Keyword
- antigen loading
- antigen-specific response
- cell therapy
- immune tolerance
- regulatory B cells (Bregs)
- regulatory T cells (Tregs)
- tolerogenic dendritic cells (tolDCs)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Dao Nyesiga, Gil ...
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Pool, Lieneke
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Englezou, Pavlos ...
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Hylander, Terese
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Ohlsson, Lars
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Appelgren, Danie ...
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show more...
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Sundstedt, Anett ...
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Tillerkvist, Kri ...
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Romedahl, Hanne ...
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Wigren, Maria
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Immunology
- Articles in the publication
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Frontiers in Imm ...
- By the university
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Malmö University
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Linköping University