Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism

Nguyen, Nam Trung; Kimura, Akihiro; Nakahama, Taisuke; Chinen, Isao; Masuda, Kouji; Nohara, Keiko; Fujii‐Kuriyama, Yoshiaki; Kishimoto, Tadamitsu

doi:10.1073/pnas.1014465107

Cited by 591 publications

(568 citation statements)

References 48 publications

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“…Using similar particles, although loaded with PLP 139-151 , the authors also showed that subcutaneous injection could reduce the incidence of EAE; however, unlike intravenous infusion, protection was not 100% [5,94]. Another strategy that focuses on altering DC phenotype is the administration of NPs that agonize the ligand-activated transcription factor aryl hydrocarbon receptor [7,[95][96][97]. The activation of aryl hydrocarbon receptor on DCs supports their differentiation into tolerogenic APCs, which supports the expansion of Tregs [95][96][97].…”

Section: Np Development For Tolerancementioning

confidence: 99%

“…Another strategy that focuses on altering DC phenotype is the administration of NPs that agonize the ligand-activated transcription factor aryl hydrocarbon receptor [7,[95][96][97]. The activation of aryl hydrocarbon receptor on DCs supports their differentiation into tolerogenic APCs, which supports the expansion of Tregs [95][96][97]. Using the MOG or PLP EAE model, pegylated gold NPs loaded with the aryl hydrocarbon receptor agonist 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester and MOG or PLP were tested for their ability to ameliorate disease [7].…”

Section: Np Development For Tolerancementioning

confidence: 99%

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Harnessing Nanoparticles for Immune Modulation

Getts¹,

Shea²,

Miller³

et al. 2016

Trends in Immunology

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Recent approaches using nanoparticles engineered for immune regulation have yielded promising results in preclinical models of disease. The number of nanoparticle therapies is growing, fueled by innovations in nanotechnology and advances in understanding of the underlying pathogenesis of immune-mediated diseases. In particular, recent mechanistic insight into the ways in which nanoparticles interact with the mononuclear phagocyte system and impact its function during homeostasis and inflammation have highlighted the potential of nanoparticle-based therapies for controlling severe inflammation while concurrently restoring peripheral immune tolerance in autoimmune disease. Here we review recent advances in nanoparticle-based approaches aimed at immune-modulation, and discuss these in the context of concepts in polymeric nanoparticle development, including particle modification, delivery and the factors associated with successful clinical deployment.

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Section: Np Development For Tolerancementioning

confidence: 99%

Section: Np Development For Tolerancementioning

confidence: 99%

Harnessing Nanoparticles for Immune Modulation

Getts¹,

Shea²,

Miller³

et al. 2016

Trends in Immunology

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show abstract

“…Mice with a poor-affinity AHR suffer from exacerbated autoimmune encephalomyelitis in the absence of an exogenous ligand 26 , and Trp catabolites suppress autoimmune neuroinflammation 29,30 , suggesting that activation of Trp catabolism represents an endogenous feedback loop to restrict inflammation through the AHR. In fact, exogenous Kyn is involved in the regulation of immune cells in mice through the AHR 31,32 . Kyn concentrations sufficient to activate the AHR are also generated by IDO in response to inflammatory stimuli (Supplementary Fig.…”

Section: Article Researchmentioning

confidence: 99%

An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor

Opitz

Litzenburger

Sahm

et al. 2011

Nature

1,563

1,534

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“…41,[117][118][119][120][121][122][123] Indeed, AHR activation boosts the ability of DCs to promote the differentiation and expansion of FoxP3 þ Tregs. 41,[118][119][120] These effects involve at least two types of tolerogenic metabolites: (1) Kynurenins. AHR activation upregulates the expression of IDO in DCs, 119,120 which catalyzes the production of kynurenine.…”

Section: Aryl Hydrocarbon Receptor (Ahr)mentioning

confidence: 99%

“…41,[118][119][120] These effects involve at least two types of tolerogenic metabolites: (1) Kynurenins. AHR activation upregulates the expression of IDO in DCs, 119,120 which catalyzes the production of kynurenine. (2) RA.…”

Section: Aryl Hydrocarbon Receptor (Ahr)mentioning

confidence: 99%

Role and therapeutic value of dendritic cells in central nervous system autoimmunity

2014

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Dendritic cells (DCs) are professional antigen-presenting cells that control the generation of adaptive immunity. Consequently, DCs have a central role in the induction of protective immunity to pathogens and also in the pathogenic immune response responsible for the development and progression of autoimmune disorders. Thus the study of the molecular pathways that control DC development and function is likely to result in new strategies for the therapeutic manipulation of the immune response. In this review, we discuss the role and therapeutic value of DCs in autoimmune diseases, with a special focus on multiple sclerosis. Cell Death and Differentiation (2015) 22, 215-224; doi:10.1038/cdd.2014; published online 29 August 2014 FactsDendritic cells (DCs) control central and peripheral tolerance through their effects on effector and regulatory T cells. Specific signaling pathways regulate the ability of different DC populations to promote effector and regulatory T-cell responses. Abnormalities in DC numbers, recruitment and function contribute to the pathology of multiple sclerosis (MS) and can be partially overcome by the use of disease-modifying therapies and the targeting of specific molecular pathways. Nanotechnology provides new tools for the modulation of DC activity in vivo and the therapeutic induction of antigenspecific tolerance in immune-mediated disorders. Open QuestionsAlthough DC populations that promote the development of forkhead box P3-positive (FoxP3 þ ) regulatory T cells (Tregs) have been identified, it is not yet clear whether these populations constitute separate tolerogenic DC lineages or represent alternative activation or maturation states of other DC populations. What are the different molecular pathways that control the DC's ability to prime effector or tolerogenic T-cell responses?There is an unmet clinical need for the development of methods for the efficient and consistent generation of tolerogenic DCs in vitro and in vivo that can be implemented in large-scale clinical setups.Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that control the activation and polarization of T cells into specific lineages and, consequently, the generation of antigen-specific antibody and T-cell responses. 1 In the context of an infectious challenge, the induction of pathogenspecific immune responses provides protective immunity to fight the infection. However, in the context of autoimmune diseases DCs regulate the balance between pathogenic and regulatory immune mechanisms, controlling disease onset and progression. Thus, DCs have a central role in the control of the adaptive immune response to pathogens and selftissues and therefore constitute potential targets for the therapeutic modulation of the immune response. In this review, we discus the role of DCs in autoimmune diseases, with a special emphasis on their role in the modulation of central nervous system (CNS) inflammation in MS. Received 12.6.14; accepted 23.6.14; Edited by H-U Simon; published online 29.8.14 Abbreviations: A...

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Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism

Cited by 591 publications

References 48 publications

Harnessing Nanoparticles for Immune Modulation

Harnessing Nanoparticles for Immune Modulation

An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor

Role and therapeutic value of dendritic cells in central nervous system autoimmunity

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