Lesional dendritic cells in patients with chronic atopic dermatitis and psoriasis exhibit parallel ability to activate T-cell subsets

Fujita, Hideki; Shemer, Avner; Suárez‐Fariñas, Mayte; Johnson-Huang, Leanne M.; Tintle, Suzanne J.; Cardinale, Irma; Fuentes‐Duculan, Judilyn; Novitskaya, Inna; Carucci, John A.; Krueger, James G.; Guttman‐Yassky, Emma

doi:10.1016/j.jaci.2011.05.016

Cited by 125 publications

(117 citation statements)

References 56 publications

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“…Often a miRNA has hundreds of different target genes, regulating biological functions through the modulation of their expression (9,10). Several miRNAs have been identified to have important and specific functions in the skin, both in keratinocytes (11)(12)(13)(14)(15)(16) and in other cell types (17,18), showing the relevance of this class of molecules in skin biology.…”

Section: Conflict Of Interestsmentioning

confidence: 99%

Increased expression of the aryl hydrocarbon receptor in patients with chronic inflammatory skin diseases

Kim

Chung

et al. 2014

Experimental Dermatology

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Th2-and Th22-polarising cytokines became statistically significant in cells from atopic patients relative to those from healthy controls. Fujita et al. (14) also confirmed the pluripotent Th-cell (Th1, Th2, Th17, Th22)-polarising capacity of freshly isolated skin-derived resident and inflammatory DCs, and they emphasised that the recruitment of disease-specific Th subsets is determined primarily by the microenvironment associated with chronic inflammation in AD. In an analogous experimental system, Reefer et al. (19) demonstrated that in DC-T cell co-cultures after TSLP, allergen or SEB stimulation, Th cells from AD patients produce Th2-type cytokines, although that study did not investigate Th22 cytokine expression. In our experiments, we also observed that unstimulated mDCs had a similar capacity to polarise Th1 cells in atopic and non-atopic individuals; however, this ability of atopic mDCs became impaired after stimulation. Consistent with the results of our study, Lebre et al. (20) found that CD1c+ DCs exhibit aberrant functions in AD patients because these cells could not induce a Th1 immune response, even in the presence of a strong Th1 stimulus.Due to the prevalent initiator but complex nature of mDCs in the skin's immune system, many therapeutic approaches target these cells via modifications of their function or the surrounding tissue microenvironment, that is, topical treatment of AD with calcineurin inhibitors and corticosteroids (21,22). Therefore, it is important to develop methods that are suitable for the investigation of the direct effects of newly developed therapies on DCs. Consequently, we want to emphasise a third point: that LSC is a useful technique to monitor mDC functions in vitro. ConclusionsBecause of the low number of mDCs in the peripheral blood and the limited blood sample volume that is available, especially in childhood, it is challenging to directly investigate the function of these cells from patients. To our knowledge, we are the first to directly determine the intracellular cytokine profile and activation of circulating mDCs in AD patients using multiparametric laser scanning cytometry (LSC). Measurements utilising this slide-based technique allow for the analysis of specimens with low cell numbers (10 5 or less) but provide results with statistical relevance. Author contributions GN performed the research, did the LSC measurement, analysed the data and wrote the manuscript; DM and ZSB did the LSC measurement and analysed the data; KG contributed the blood samples, GM, AK and TD contributed to the research design, EGY, ER supervised the study, TB supervised the study and edited the manuscript, ASZ designed the study, wrote the manuscript and supervised the research group. Acknowledgements Conflict of interestsThe authors have declared no conflicting interests. Supporting InformationAdditional Supporting Information may be found in the online version of this article: Appendix S1. Materials and methods. Table S1. Data on patients, activation and maturation markers and cytok...

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Section: Conflict Of Interestsmentioning

confidence: 99%

Increased expression of the aryl hydrocarbon receptor in patients with chronic inflammatory skin diseases

Kim

Chung

et al. 2014

Experimental Dermatology

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“…In addition to detecting the activation of mDCs (DAPI, CD83, CD86 staining), our aim was to analyse combinations of mDC-derived cytokines/chemokines that have well-characterised roles in the lineage commitment of the different Th cell subtypes, that is, IL-12 indicates Th1 polarisation; IL-2, IL-4 and CCL17 indicate Th2 polarisation (13,14); IL-6 and TNFa indicate Th22 polarisation (15,16); TGFb1, IL-23 and IL-6 indicate Th17 polarisation (17); and TGFb1 and IL-10 indicate Treg polarisation (18) (Appendix S1).…”

Section: Experimental Designmentioning

confidence: 99%

The atopic skin‐like microenvironment modulates the T‐cell‐polarising cytokine production of myeloid dendritic cells, as determined by laser scanning cytometry

Nagy

Doan-Xuan

Gáspár

et al. 2014

Experimental Dermatology

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Because it is not known exactly when or where myeloid dendritic cells (mDCs) acquire their atopic dermatitis (AD)-specific T-cell-polarising ability in patients with this condition, we used laser scanning cytometry (LSC) to determine whether isolated peripheral blood mDCs from AD patients differed from cells from controls in their cytokine expression profiles de novo and after stimulation with Staphylococcus enterotoxin B (SEB) and thymic stromal lymphopoietin (TSLP), which represents an ADlike microenvironment. Unstimulated mDCs from AD patients showed pluripotent T-cell-polarising capacity, and the surrounding skin microenvironment was essential for the distinctive, disease-specific activity of mDCs (Th2-Th22 bias). We also emphasise that LSC is an attractive technique to study the effect of new DC-targeted therapeutic modalities in AD.

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“…Epidermal and dermal single-cell suspensions from healthy skin donors were obtained after separation of the epidermis and dermis as described [16]. Skin cell suspensions were stained with the following antibodies: FITC-HLA-DR and PE-anti-CD1a, and anti-gal-1, anti-gal-3 or anti-gal-9 followed by Alexa fluor 647-DAG for epidermal cells and Pacific blue-CD11c, Pacific orange-CD45, FITC-HLA-DR for dermal cells.…”

Section: Flow Cytometry and Cell Sortingmentioning

confidence: 99%

“…2B). Recently, it has been described that a subpopulation of inflammatory dendritic epidermal cells (IDECs) are CD1a+ [16]. In order to assess the expression of gal-1 specifically in LC, three-color immunostaining was performed in skin samples (Fig.…”

Section: Gal-1 Expression Is Reduced In Langerhans Cells From Psoriasmentioning

confidence: 99%

Psoriasis in humans is associated with down‐regulation of galectins in dendritic cells

Fuente

Pérez‐Gala

Bonay

et al. 2012

The Journal of Pathology

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2 ABSTRACT.We have investigated the expression and role of galectin-1 and other galectins in psoriasis and in the Th1/Th17 effector and dendritic cell responses associated with this chronic inflammatory skin condition. To determine differences between psoriasis patients and healthy donors, galectins expression was analyzed by RT-PCR assays in skin samples and specifically on epidermal and peripheral blood dendritic cells by immunofluorescence and flow cytometry.In skin of healthy donors galectins 1, 3 and 9 were expressed in a high proportion of Langerhans cells. Also, galectins were differentially expressed in peripheral blood dendritic cell subsets; galectin-1 and galectin-9 were highly expressed in peripheral myeloid dendritic cells compared with plasmacytoid dendritic cells. We found that non-lesional as well as lesional skin samples from psoriasis patients had low levels of galectin-1 at mRNA and protein level in parallel with low levels of IL-10 mRNA compared with skin from healthy patients. However, only lesional skin samples expressed high levels of

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Lesional dendritic cells in patients with chronic atopic dermatitis and psoriasis exhibit parallel ability to activate T-cell subsets

Cited by 125 publications

References 56 publications

Increased expression of the aryl hydrocarbon receptor in patients with chronic inflammatory skin diseases

Increased expression of the aryl hydrocarbon receptor in patients with chronic inflammatory skin diseases

The atopic skin‐like microenvironment modulates the T‐cell‐polarising cytokine production of myeloid dendritic cells, as determined by laser scanning cytometry

Psoriasis in humans is associated with down‐regulation of galectins in dendritic cells

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