Dataset Information

Activation of Human Mucosal-Associated Invariant T Cells Induces CD40L-Dependent Maturation of Monocyte-Derived and Primary Dendritic Cells.

ABSTRACT: Mucosal-associated invariant T (MAIT) cells are innate T cells that recognize intermediates of the vitamin B2 biosynthetic pathway presented by the monomorphic MR1 molecule. It remains unclear whether, in addition to their cytolytic activity that is important in antimicrobial defense, MAIT cells have immune-modulatory functions that could enhance dendritic cell (DC) maturation. In this study, we investigated the molecular mechanisms dictating the interactions between human MAIT cells and DCs and demonstrate that human MAIT cells mature monocyte-derived and primary DCs in an MR1- and CD40L-dependent manner. Furthermore, we show that MAIT cell-derived signals synergize with microbial stimuli to induce secretion of bioactive IL-12 by DCs. Activation of human MAIT cells in whole blood leads to MR1- and cytokine-dependent NK cell transactivation. Our results underscore an important property of MAIT cells, which can be of translational relevance to rapidly orchestrate adaptive immunity through DC maturation.

SUBMITTER: Salio M

PROVIDER: S-EPMC5632842 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Activation of Human Mucosal-Associated Invariant T Cells Induces CD40L-Dependent Maturation of Monocyte-Derived and Primary Dendritic Cells.

Salio Mariolina M Gasser Olivier O Gonzalez-Lopez Claudia C Martens Anne A Veerapen Natacha N Gileadi Uzi U Verter Jacob G JG Napolitani Giorgio G Anderson Regan R Painter Gavin G Besra Gurdyal S GS Hermans Ian F IF Cerundolo Vincenzo V

Journal of immunology (Baltimore, Md. : 1950) 20170906 8

Mucosal-associated invariant T (MAIT) cells are innate T cells that recognize intermediates of the vitamin B2 biosynthetic pathway presented by the monomorphic MR1 molecule. It remains unclear whether, in addition to their cytolytic activity that is important in antimicrobial defense, MAIT cells have immune-modulatory functions that could enhance dendritic cell (DC) maturation. In this study, we investigated the molecular mechanisms dictating the interactions between human MAIT cells and DCs and ...[more]

PMID: 28877992

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Project description:Allogeneic cell-based therapies using adipose tissue-derived stromal cells (ASCs) offer an off-the-shelf alternative to autologous therapy. An underlying assumption is that ASC can modulate the immune response of the recipient. However, in vitro models are required to explore and identify cell interactions and mechanisms of action, to ensure sufficient and sustained effects, and to document these. In this study, we shed light on the effect of ASC manufactured for clinical use on monocyte-derived dendritic cells and an inflammatory microenvironment. ASCs were isolated from healthy voluntary donors, expanded using a human platelet lysate in bioreactors, and cryopreserved as per clinical use. Monocyte-derived dendritic cells were generated by isolation of monocytes and differentiation with GM-CSF and IL-4. Dendritic cells were cocultured with different ratios of ASC and matured with LPS and IFN-γ. Dexamethasone was included as an immunosuppressive control. Dendritic cells were analyzed by flow cytometry for CD11c, CD40, CD80, CD83, CD86, PD-L1, and HLA-DR, and supernatants were analyzed for FGF2, HGF, IL-10, IL-12p70, LIF, MIF, PDGF, PlGF, and IDO. Reduced expression of maturation markers was observed on ASC-treated dendritic cells, while high levels of PD-L1 were maintained. Interestingly, the expression of CD83 was elevated. Escalating ratios of ASC did not affect the concentration of IL-10 considerably, whereas the presence of IL-12 was reduced in a dose-dependent manner. Besides offsetting the IL-12/IL-10 balance, the concentrations of IDO and MIF were elevated in cocultures. Concentrations of FGF2, HGF, LIF, and PIGF were high in ASC cocultures, whereas PDGF was depleted. In a robust coculture model, the addition of ASC to dendritic cells inhibited the dendritic maturation substantially, while inducing a less inflammatory and more tolerogenic milieu. Despite the exposure to dendritic cells and inflammatory stimuli, ASC resulted in supernatants with trophic factors relevant for regeneration. Thus, ASC can perform immunomodulation while providing a regenerative environment.

Dataset Information

Activation of Human Mucosal-Associated Invariant T Cells Induces CD40L-Dependent Maturation of Monocyte-Derived and Primary Dendritic Cells.

Publications

Activation of Human Mucosal-Associated Invariant T Cells Induces CD40L-Dependent Maturation of Monocyte-Derived and Primary Dendritic Cells.

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