Fast dendritic cells matured with Poly (I:C) may acquire tolerogenic properties

Pavlović, Bojan; Tomić, Sergej; Đokić, Jelena; Vasilijić, Saša; Vučević, Dragana; Lukić, Jovanka; Gruden-Movsesijan, Alisa; Ilić, Nataša; Marković, Milan; Čolić, Miodrag

doi:10.1016/j.jcyt.2015.08.001

Cited by 7 publications

(11 citation statements)

References 56 publications

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“…Since DCs upon the treatment with ES L1 antigens acquire semi-mature phenotype, limited allo-stimulatory capacity, and shift the immune response toward Th2 and regulatory type, we presumed that ES L1-treated DCs possess tolerogenic properties. In addition to reduced pro-inflammatory phenotype and functions, the tolerogenic DCs express tolerogenic markers, such as IDO-1 and ILT-3, and display an increased capacity to induce Tregs ( 56 , 57 ). Therefore, we first analyzed the expression of IDO-1 and ILT-3 by DCs under the influence of ES L1 antigens, in the presence or absence of additional stimulation with LPS/IFN-γ (Figures 4 A,B).…”

Section: Resultsmentioning

confidence: 99%

“…A number of studies have dealt with in vitro generation of DCs from monocytes that can be manipulated to acquire tolerogenic properties ( 35 , 56 , 58 – 60 ). These cells were shown to have an immature or semi-mature phenotype, low production of inflammatory and increased production of anti-inflammatory cytokines, the ability to present antigens in a tolerogenic form, and consequently, an increased capacity to induce Tregs.…”

Section: Discussionmentioning

confidence: 99%

“…In line with this, ES L1-treated DCs displayed the resistance to the maturation induced by both TLR3 (Poly I:C) and TLR4 (LPS) agonist in particular. In contrast to Poly (I:C) and LPS, known to induce predominantly Th1 ( 56 ) and a mixed Th1/Th2 response ( 69 ), respectively, LPS/IFN-γ cocktail is known to induce inflammatory type 1 DCs ( 52 ), which are able to induce both Th1- and Th17-mediated immune response ( 50 ). Both, Th1 and Th17 cells were shown to be critically involved in the pathogenesis of chronic inflammation and autoimmunity ( 70 ).…”

Section: Discussionmentioning

confidence: 99%

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Trichinella spiralis Excretory–Secretory Products Induce Tolerogenic Properties in Human Dendritic Cells via Toll-Like Receptors 2 and 4

et al. 2018

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Trichinella spiralis, as well as its muscle larvae excretory–secretory products (ES L1), given either alone or via dendritic cells (DCs), induce a tolerogenic immune microenvironment in inbred rodents and successfully ameliorate experimental autoimmune encephalomyelitis. ES L1 directs the immunological balance away from T helper (Th)1, toward Th2 and regulatory responses by modulating DCs phenotype. The ultimate goal of our work is to find out if it is possible to translate knowledge obtained in animal model to humans and to generate human tolerogenic DCs suitable for therapy of autoimmune diseases through stimulation with ES L1. Here, the impact of ES L1 on the activation of human monocyte-derived DCs is explored for the first time. Under the influence of ES L1, DCs acquired tolerogenic (semi-matured) phenotype, characterized by low expression of HLA-DR, CD83, and CD86 as well as moderate expression of CD40, along with the unchanged production of interleukin (IL)-12 and elevated production of IL-10 and transforming growth factor (TGF)-β, compared to controls. The interaction with DCs involved toll-like receptors (TLR) 2 and 4, and this interaction was mainly responsible for the phenotypic and functional properties of ES L1-treated DCs. Importantly, ES L1 potentiated Th2 polarizing capacity of DCs, and impaired their allo-stimulatory and Th1/Th17 polarizing properties. Moreover, ES L1-treated DCs promoted the expansion of IL-10- and TGF-β- producing CD4+CD25hiFoxp3hi T cells in indolamine 2, 3 dioxygenase (IDO)-1-dependent manner and increased the suppressive potential of the primed T cell population. ES L1-treated DCs retained the tolerogenic properties, even after the challenge with different pro-inflammatory stimuli, including those acting via TLR3 and, especially TLR4. These results suggest that the induction of tolerogenic properties of DCs through stimulation with ES L1 could represent an innovative approach for the preparation of tolerogenic DC for treatment of inflammatory and autoimmune disorders.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Trichinella spiralis Excretory–Secretory Products Induce Tolerogenic Properties in Human Dendritic Cells via Toll-Like Receptors 2 and 4

et al. 2018

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“…CD1a + DC were shown to produce more IL-12 and induce Th1 polarization, 46 whereas CD1a -DC displayed a weaker maturation potential and a higher capacity to produce IL-10 and regulatory T cells. 47 Such an effect of nCNF from a different source, 31 as well as other nanomaterials 34,36 and cultivation procedures, 24,48 was described previously by our group. Therefore, the ratio between CD1a + and CD1a -DC might be a good indicator of DC tolerogenicity.…”

Section: Discussionmentioning

confidence: 99%

Functionalization-dependent effects of cellulose nanofibrils on tolerogenic mechanisms of human dendritic cells

Tomić

Ilić

Kokol

et al. 2018

IJN

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BackgroundCellulose nanofibrils (CNF) are attractive nanomaterials for various biomedical applications due to their excellent biocompatibility and biomimetic properties. However, their immunoregulatory properties are insufficiently investigated, especially in relation to their functionalization, which could cause problems during their clinical application.MethodsUsing a model of human dendritic cells (DC), which have a central role in the regulation of immune response, we investigated how differentially functionalized CNF, ie, native (n) CNF, 2,2,6,6-tetramethylpiperidine 1-oxyl radical-oxidized (c) CNF, and 3-aminopropylphosphoric acid-functionalized (APAc) CNF, affect DC properties, their viability, morphology, differentiation and maturation potential, and the capacity to regulate T cell-mediated immune response.ResultsNontoxic doses of APAcCNF displayed the strongest inhibitory effects on DC differentiation, maturation, and T helper (Th) 1 and Th17 polarization capacity, followed by cCNF and nCNF, respectively. These results correlated with a specific pattern of regulatory cytokines production by APAcCNF-DC and their increased capacity to induce suppressive CD8+CD25+IL-10+ regulatory T cells in immunoglobulin-like transcript (ILT)-3- and ILT-4- dependent manner. In contrast, nCNF-DC induced predominantly suppressive CD4+CD25hiFoxP3hi regulatory T cells in indolamine 2,3-dioxygenase-1-dependent manner. Different tolerogenic properties of CNF correlated with their size and APA functionalization, as well as with different expression of CD209 and actin bundles at the place of contact with CNF.ConclusionThe capacity to induce different types of DC-mediated tolerogenic immune responses by functionalized CNF opens new perspectives for their application as well-tolerated nanomaterials in tissue engineering and novel platforms for the therapy of inflammatory T cell-mediated pathologies.

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“…Additionally, the immunostimulant TLR3 ligand polyinosinic:polycytidylic acid (poly I:C) has also been reported to induce human tolDC, although in an inconsistent and poorly efficient manner. Nevertheless, the differential up-modulation of both IDO1 and PD-L1 , two genes involved in the induction and maintenance of immune tolerance, has been confirmed by quantitative PCR for these cells ( 56 , 57 ). As for tolDC induced with hydrocortisone and clobetasol-17-propionate, no transcriptomic biomarkers have been reported.…”

Section: Tolerogenic Dendritic Cells As Key Tolerance-inducing Playermentioning

confidence: 94%

Searching for the Transcriptomic Signature of Immune Tolerance Induction—Biomarkers of Safety and Functionality for Tolerogenic Dendritic Cells and Regulatory Macrophages

2018

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The last years have witnessed a breakthrough in the development of cell-based tolerance-inducing cell therapies for the treatment of autoimmune diseases and solid-organ transplantation. Indeed, the use of tolerogenic dendritic cells (tolDC) and regulatory macrophages (Mreg) is currently being tested in Phase I and Phase II clinical trials worldwide, with the aim of finding an effective therapy able to abrogate the inflammatory processes causing these pathologies without compromising the protective immunity of the patients. However, there exists a wide variety of different protocols to generate human tolDC and Mreg and, consequently, the characteristics of each product are heterogeneous. For this reason, the identification of biomarkers able to define their functionality (tolerogenicity) is of great relevance, on the one hand, to guarantee the safety of tolDC and Mreg before administration and, on the other hand, to compare the results between different cell products and laboratories. In this article, we perform an exhaustive review of protocols generating human tolDC and Mreg in the literature, aiming to elucidate if there are any common transcriptomic signature or potential biomarkers of tolerogenicity among the different approaches. However, and although several effectors seem to be induced in common in some of the most reported protocols to generate both tolDC or Mreg, the transcriptomic profile of these cellular products strongly varies depending on the approach used to generate them.

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Fast dendritic cells matured with Poly (I:C) may acquire tolerogenic properties

Cited by 7 publications

References 56 publications

Trichinella spiralis Excretory–Secretory Products Induce Tolerogenic Properties in Human Dendritic Cells via Toll-Like Receptors 2 and 4

Trichinella spiralis Excretory–Secretory Products Induce Tolerogenic Properties in Human Dendritic Cells via Toll-Like Receptors 2 and 4

Functionalization-dependent effects of cellulose nanofibrils on tolerogenic mechanisms of human dendritic cells

Searching for the Transcriptomic Signature of Immune Tolerance Induction—Biomarkers of Safety and Functionality for Tolerogenic Dendritic Cells and Regulatory Macrophages

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