Nickel and DNCB Induce CCR7 Expression on Human Dendritic Cells Through Different Signalling Pathways: Role of TNF-α and MAPK

Boislevé, Fanny; Kerdine-Römer, Saadia; Rougier-Larzat, Nathalie; Pallardy, Marc

doi:10.1111/j.0022-202x.2004.23229.x

Cited by 112 publications

(91 citation statements)

References 47 publications

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“…Sensitizers have also been demonstrated to induce the expression of markers related to function and maturation of DCs, the production of proinflammatory cytokines, and the phosphorylation of members of the MAPK family and NF-kB pathway, thus mimicking the effects of danger signals (9)(10)(11)(31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

“…During the sensitization phase, skin dendritic cells (DCs) capture the metal bound to self-protein, migrate through the lymphatic vessels, and present the haptenprotein complex to naive T cells in the draining lymph node (7,8). Moreover, using human in vitro DC models, several groups have showed that chemical sensitizer treatment can induce phenotypic modifications with HLA-DR, CD86, CD40, CD83, and CCR7 upregulation and IL-12 and IL-8 production (9)(10)(11)(12).…”

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confidence: 99%

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Mechanisms of IL-12 Synthesis by Human Dendritic Cells Treated with the Chemical Sensitizer NiSO4

Antonios

Rousseau

Larangé

et al. 2010

The Journal of Immunology

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Allergic contact dermatitis, caused by metallic ions, is a T cell-mediated inflammatory skin disease. IL-12 is a 70-kDa heterodimeric protein composed of IL-12p40 and IL-12p35, playing a major role in the generation of allergen-specific T cell responses. Dendritic cells (DCs) are APCs involved in the induction of primary immune responses, as they possess the ability to stimulate naive T cells. In this study, we address the question whether the sensitizer nickel sulfate (NiSO4) itself or in synergy with other signals can induce the secretion of IL-12p70 in human monocyte-derived DCs (Mo-DCs). We found that IL-12p40 was produced by Mo-DC in response to NiSO4 stimulation. Addition of IFN-γ concomitantly to NiSO4 leads to IL-12p70 synthesis. NiSO4 treatment leads to the activation of MAPK, NF-κB pathways, and IFN regulatory factor 1 (IRF-1). We investigated the role of these signaling pathways in IL-12 production using known pharmacological inhibitors of MAPK and NF-κB pathways and RNA interference-mediated silencing of IRF-1. Our results showed that p38 MAPK, NF-κB, and IRF-1 were involved in IL-12p40 production induced by NiSO4. Moreover, IRF-1 silencing nearly totally abrogated IL-12p40 and IL-12p70 production provoked by NiSO4 and IFN-γ. In response to NiSO4, we observed that STAT-1 was phosphorylated on both serine and tyrosine residues and participated to NiSO4-induced IRF-1 activation. N-acetylcysteine abolished STAT-1 phosphorylation, suggesting that STAT-1 activation may be dependent on NiSO4-induced alteration of the redox status of the cell. These results indicate that p38 MAPK, NF-κB, and IRF-1 are activated by NiSO4 in Mo-DC and cooperate for IL-12 production.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Mechanisms of IL-12 Synthesis by Human Dendritic Cells Treated with the Chemical Sensitizer NiSO4

Antonios

Rousseau

Larangé

et al. 2010

The Journal of Immunology

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“…As immature DC, following induction of maturation after stimulation by inflammatory cytokines or haptens, up-regulate CCR7 [39,41,42], our next question was whether or not the expression of CCR7 on LC is impaired during the maturational changes following hapten application to SHPS-1 mutant mice. We found that expression of CCR7 on LC is suppressed following DNFB application in SHPS-1 mutant mice.…”

Section: Discussionmentioning

confidence: 99%

Src homology 2 domain‐containing protein tyrosine phosphatase substrate 1 regulates the induction of Langerhans cell maturation

Fukunaga

Nagai

et al. 2006

Eur J Immunol

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Recently, we reported that Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1) plays an important role in the migration of Langerhans cells (LC). Here, we show that SHPS-1 is involved in the maturation of LC. Immunofluorescence analysis on epidermal sheets for I-A or CD86 revealed that LC maturation induced by 2,4-dinitro-1-fluorobenzene (DNFB) or by TNF-a was inhibited by pretreatment with an anti-SHPS-1 monoclonal antibody (mAb) or with CD47-Fc fusion protein, a ligand for SHPS-1. Further, FACS analysis demonstrated that I-A + LC that had emigrated from skin explants expressed CD80 or CD86, whereas CD47-Fc protein reduced CD80 high+ or CD86 high+ cells. CD47-Fc protein also reduced the upregulation of surface CD80 or CD86 by LC remaining in the skin explants. In SHPS-1 mutant mice, we observed that the up-regulation of surface CD86 and CCR7 by LC induced by DNFB as well as that of surface CD80 and CD86 by LC in skin explants was attenuated. Finally, contact hypersensitivity (CHS) response was suppressed in SHPS-1 mutant mice and in wild-type mice treated with an anti-SHPS-1 mAb. These observations indicate that SHPS-1 plays an important role in the maturation of LC ex vivo and in vivo, and that SHPS-1-CD47 interaction may negatively regulate CHS. IntroductionDC are potent antigen-presenting cells that play a crucial role in the initiation of immune responses to pathogens. Langerhans cells (LC) are specialized immature DC in the skin that reside in the suprabasal layers of the epidermis. When LC encounter exogenous antigens, including haptens and microorganisms, they capture and process them to generate MHC/peptide complexes on their surface. LC migrate from the epidermis to draining lymphoid tissues in order to initiate naive T cells and to present the MHC/peptide complexes to Correspondence: Dr. Tatsuya Horikawa, Division of Dermatology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017Japan Fax:+81-78-382-6149 e-mail: thorikaw@med.kobe-u.ac.jp Received 12/1/06Revised 13/9/06 Accepted 19/10/06 [DOI 10.1002/eji.200635864] Key words: Contact hypersensitivity Á Langerhans cells Á Maturation Á Src homology 2 domaincontaining protein tyrosine phosphatase substrate 1Abbreviations: CCR7: CC chemokine receptor 7 Á CHS: contact hypersensitivity Á DNFB: 2,4-dinitro-1-fluorobenzene Á LC: Langerhans cell Á SHPS-1: Src homology 2 domaincontaining protein tyrosine phosphatase substrate 1 Á SIRP a1: signal-regulatory protein a1 and . In mice, SHPS-1 is expressed in myeloid cells, including monocytes, macrophages and DC [25]. SHPS-1 is a transmembrane glycoprotein whose extracellular domain comprises three immunoglobulin-like domains with multiple N-linked glycosylation sites, while the cytoplasmic domain of SHPS-1 contains four tyrosine residues that form two ITIM [26]. SHPS-1 was initially discovered as a tyrosine-phosphorylated transmembrane protein that binds SHP-1 or SHP-2. IAP/CD47, an integrin-associated...

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“…In human CD34 + -derived DC, nickel activates p38 MAPK, ERK1/2 and JNK, all of which are MAPKs involved in the expression of CD83, CD86 and CCR7 but not in the nickel-induced down-regulation of E-cadherin and Langerin (Boisleve et al, 2005). TNF-α production induced by DNCB was also linked to the activation of p38 MAPK and JNK (Boisleve et al, 2004). In previous results performed with the foetal skin-derived dendritic cell line (FSDC), we reported that DNFB activates p38 MAPK and ERK1/2 via the production of reactive oxygen species and that protein oxidation plays an important role in MAPKs activation (Matos et al, 2005b).…”

Section: Activation Of the Mitogen-activated Protein Kinases (Mapks)mentioning

confidence: 92%

Signal transduction profile of chemical sensitisers in dendritic cells: An endpoint to be included in a cell-based in vitro alternative approach to hazard identification?

Neves

Gonçalo

Figueiredo

et al. 2011

Toxicology and Applied Pharmacology

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The development of non-animal testing methods for the assessment of skin sensitisation potential is an urgent challenge within the framework of existing and forthcoming legislation. Efforts have been made to replace current animal tests, but so far no alternative methods have been developed. It is widely recognised that alternatives to animal testing cannot be accomplished with a single approach, but rather will require the integration of results obtained from different in vitro and in silico assays. The argument subjacent to the development of in vitro dendritic cell (DC)-based assays is that sensitiser-induced changes in the DC phenotype can be differentiated from those induced by irritants. This assumption is derived from the unique capacity of DC to convert environmental signals encountered at the skin into a receptor expression pattern (MHC class II molecules, co-stimulatory molecules, chemokine receptors) and a soluble mediator release profile that will stimulate T lymphocytes. Since signal transduction cascades precede changes in surface marker expression and cytokine/ chemokine secretion, these phenotypic modifications are a consequence of a signal transduction profile that is specifically triggered by sensitisers and not by irritants. A limited number of studies have addressed this subject and the present review attempts to summarise and highlight all of the signalling pathways modulated by skin sensitisers and irritants. Furthermore, we conclude this review by focusing on the most promising strategies suitable for inclusion into a cell-based in vitro alternative approach to hazard identification.

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Nickel and DNCB Induce CCR7 Expression on Human Dendritic Cells Through Different Signalling Pathways: Role of TNF-α and MAPK

Cited by 112 publications

References 47 publications

Mechanisms of IL-12 Synthesis by Human Dendritic Cells Treated with the Chemical Sensitizer NiSO4

Mechanisms of IL-12 Synthesis by Human Dendritic Cells Treated with the Chemical Sensitizer NiSO4

Src homology 2 domain‐containing protein tyrosine phosphatase substrate 1 regulates the induction of Langerhans cell maturation

Signal transduction profile of chemical sensitisers in dendritic cells: An endpoint to be included in a cell-based in vitro alternative approach to hazard identification?

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