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Tolerogenic dendrit...
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Dao Nyesiga, GillianMalmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces,Idogen AB, Lund, Sweden,Idogen AB, Sweden; Malmo Univ, Sweden
(författare)
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.
- Artikel/kapitelEngelska2023
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Frontiers Media S.A.2023
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:mau-63661
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https://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-63661URI
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https://doi.org/10.3389/fimmu.2023.1045183DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-199127URI
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Språk:engelska
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Sammanfattning på:engelska
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Funding Agencies|The authors declare financial support was received for the research, authorship, and/or publication of this article. This was supported by Knowledge Foundation, Horizon 2020 (grant no. 778 246), and Ingrid Asp Foundation. Funding for open access publicatio; Knowledge Foundation [778 246]; Horizon 2020; Ingrid Asp Foundation
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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.
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Biuppslag (personer, institutioner, konferenser, titlar ...)
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Pool, LienekeIdogen AB, Lund, Sweden
(författare)
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Englezou, Pavlos CIdogen AB, Lund, Sweden
(författare)
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Hylander, TereseIdogen AB, Lund, Sweden
(författare)
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Ohlsson, LarsMalmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces,Malmo Univ, Sweden(Swepub:mau)hslabr
(författare)
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Appelgren, DanielLinköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten(Swepub:liu)danso84
(författare)
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Sundstedt, AnetteIdogen AB, Lund, Sweden
(författare)
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Tillerkvist, KristinaIdogen AB, Lund, Sweden
(författare)
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Romedahl, Hanne RIdogen AB, Lund, Sweden
(författare)
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Wigren, MariaIdogen AB, Lund, Sweden
(författare)
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Malmö universitetInstitutionen för biomedicinsk vetenskap (BMV)
(creator_code:org_t)
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Ingår i:Frontiers in Immunology: Frontiers Media S.A.141664-3224
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