Therapeutic potential of semi-mature dendritic cells for tolerance induction

Lutz, Manfred B.

doi:10.3389/fimmu.2012.00123

Cited by 77 publications

(64 citation statements)

References 116 publications

(147 reference statements)

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“…In line with our results, NouriShirazi and Guinet [29] proposed that nicotine can exert immunosuppressive effect on immune surveillance through functional impairment of the DC system. Tolerogenic DC are characterized by a semimature phenotype, with low levels of co-stimulatory molecules expression [30]. Moreover, tolerogenic DC produce high levels of anti-inflammatory cytokines resulting in the induction and expansion of regulatory T cells [30].…”

Section: Discussionmentioning

confidence: 99%

“…Tolerogenic DC are characterized by a semimature phenotype, with low levels of co-stimulatory molecules expression [30]. Moreover, tolerogenic DC produce high levels of anti-inflammatory cytokines resulting in the induction and expansion of regulatory T cells [30]. Precisely, the increment in DC-derived IL-10 levels produced by autoAbs added to the inhibition of HLA-DR and CD86 expression could be contributing to the down-regulation of Th1 response and to the up-regulation of Th2 profile with a positive loop on B cells.…”

Section: Discussionmentioning

confidence: 99%

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Cholinergic Actions of Autoantibodies from Breast Cancer Patients on Dendritic Cells

Lombardi¹

2015

J Clin Cell Immunol

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Autoantibodies (autoAbs) against self-proteins have been localized in tumor microenvironment exerting a complex network of interactions. We reported the presence of autoAbs in breast cancer patients, which promote tumor progression by activating muscarinic acetylcholine receptors (mAChR) in tumor cells. Cholinergic receptors are also expressed in dendritic cells (DC) and much clear evidence demonstrated a deficient functional activity of DC in cancer. Here we investigated whether autoAbs can modulate the expression of maturation markers and the production of cytokines by DC. IgG from breast cancer patients in stage I reduced the expression of HLA-DR and CD86 as well as tumor necrosis factor alpha liberation and augmented interleukin IL-12 and IL-10 levels by cholinergic activation of mature DC. The latter cytokines are also up-regulated in patients' sera, probably due to tumor influence, since the addition of breast tumor extract increased cytokine levels in immature DC reaching levels of mature DC mainly for IL-10 and IL-12. It could be assumed that autoAbs are reinforcing the tolerogenic/ immunosuppressive profile mediated by DC in breast cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cholinergic Actions of Autoantibodies from Breast Cancer Patients on Dendritic Cells

Lombardi¹

2015

J Clin Cell Immunol

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“…Although potently capable of initiating adaptive immune responses, DCs also play an important role in modulating the induction of tolerance (3)(4)(5). Tolerogenic DCs (tDCs) are generally characterized by an immature or semimature phenotype, with a capacity for high Ag uptake and low expression of costimulatory molecules (2,6). Additionally, tDCs produce low amounts of proinflammatory cytokines and high amounts of anti-inflammatory cytokines.…”

Section: Endritic Cells (Dcs) Are a Heterogeneous Population Ofmentioning

confidence: 99%

Protein Kinase C Inhibitor Generates Stable Human Tolerogenic Dendritic Cells

Matsumoto

Hasegawa

Onishi

et al. 2013

The Journal of Immunology

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Tolerogenic dendritic cells (DCs) are a promising tool for a specific form of cellular therapy whereby immunological tolerance can be induced in the context of transplantation and autoimmunity. From libraries of bioactive lipids, nuclear receptor ligands, and kinase inhibitors, we screened conventional protein kinase C inhibitors (PKCIs) bisindolylmaleimide I, Gö6983, and Ro32-0432 with strong tolerogenic potential. PKCI-treated human DCs were generated by subjecting them to a maturation process after differentiation of immature DCs. The PKCI-treated DCs had a semimature phenotype, showing high production of IL-10, and efficiently induced IL-10–producing T cells and functional Foxp3+ regulatory T cells from naive CD4+ T cells, thus eliciting a strong immunosuppressive function. They also showed CCR7 expression and sufficient capacity for migration toward CCR7 ligands. Additionally, PKCI-treated DCs were highly stable when exposed to inflammatory stimuli such as proinflammatory cytokines or LPS. Conventional PKCIs inhibited NF-κB activation of both the canonical and noncanonical pathways of DC maturation, thus suppressing the expression of costimulatory molecules and IL-12 production. High production of IL-10 in PKCI-treated DCs was due to not only an increase of intracellular cAMP, but also a synergistic effect of increased cAMP and NF-κB inhibition. Moreover, PKCI-treated mouse DCs that had properties similar to PKCI-treated human DCs prevented graft-versus-host disease in a murine model of acute graft-versus-host disease. Conventional PKCI-treated DCs may be useful for tolerance-inducing therapy, as they satisfy the required functional characteristics for clinical-grade tolerogenic DCs.

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“…38,39 These regulatory pDCs exhibit a semimature phenotype and are more likely than imDCs to induce the generation of Tregs, Meanwhile, pDCs change much less than imDCs in vivo after exposure to an inflammatory microenvironment. 40 The concept that pDCs have the potential to promote graft tolerance has emerged recently. [41][42][43] One potential explanation for this phenomenon is that pDCs can induce IL-10-producing T cells via ICOS-ICOSL (B7RP-1) interactions.…”

Section: The Induction Of Tol-dcsmentioning

confidence: 99%

Tolerogenic dendritic cells and their applications in transplantation

Shi

2014

Cell Mol Immunol

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In transplantation immunology, the ultimate goal is always to successfully and specifically induce immune tolerance of allografts. Tolerogenic dendritic cells (tol-DCs) with immunoregulatory functions have attracted much attention as they play important roles in inducing and maintaining immune tolerance. Here, we focused on tol-DCs that have the potential to promote immune tolerance after solid-organ transplantation. We focus on their development and interactions with other regulatory cells, and we also explore various tol-DC engineering protocols. Harnessing tol-DCs represents a promising cellular therapy for promoting long-term graft functional survival in transplant recipients that will most likely be achieved in the future.

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Therapeutic potential of semi-mature dendritic cells for tolerance induction

Cited by 77 publications

References 116 publications

Cholinergic Actions of Autoantibodies from Breast Cancer Patients on Dendritic Cells

Cholinergic Actions of Autoantibodies from Breast Cancer Patients on Dendritic Cells

Protein Kinase C Inhibitor Generates Stable Human Tolerogenic Dendritic Cells

Tolerogenic dendritic cells and their applications in transplantation

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