Keratinocytes under Fire of Proinflammatory Cytokines: Bona Fide Innate Immune Cells Involved in the Physiopathology of Chronic Atopic Dermatitis and Psoriasis

Bernard, François‐Xavier; Morel, Franck; Camus, Magalie; Pedretti, Nathalie; Barrault, C.; Garnier, Julien; Lecron, Jean‐Claude

doi:10.1155/2012/718725

Cited by 89 publications

(84 citation statements)

References 68 publications

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“…In the present study, it was first established that NHK stimulated for 24 h with poly I:C and cytokines (TNFα, IL-4, and IL-13) constituted a model mimicking an “AD-like” condition 26. Indeed, keratinocyte differentiation markers such as involucrin, which were decreased in the present study, are important for skin barrier formation and integrity.…”

Section: Discussionmentioning

confidence: 51%

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Anti-inflammatory and immunomodulatory effects of <em>Aquaphilus dolomiae</em> extract on in vitro models

Ariès

Hernandez-Pigeon

Vaissiere

et al. 2016

CCID

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BackgroundAtopic dermatitis (AD) is a common skin disease characterized by recurrent pruritic inflammatory skin lesions resulting from structural and immune defects of the skin barrier. Previous studies have shown the clinical efficacy of Avène thermal spring water in AD, and a new microorganism, Aquaphilus dolomiae was suspected to contribute to these unique properties. The present study evaluated the anti-inflammatory, antipruritic, and immunomodulatory properties of ES0, an original biological extract of A. dolomiae, in immune and inflammatory cell models in order to assess its potential use in the treatment of AD.Materials and methodsAn ES0 extract containing periplasmic and membrane proteins, peptides, lipopolysaccharides, and exopolysaccharides was obtained from A. dolomiae. The effects of the extract on pruritus and inflammatory mediators and immune mechanisms were evaluated by using various AD cell models and assays.ResultsIn a keratinocyte model, ES0 inhibited the expression of the inflammatory mediators, thymic stromal lymphopoietin, interleukin (IL)-18, IL-4R, IL-8, monocyte chemoattractant protein-3, macrophage inflammatory protein-3α, and macrophage-derived chemokine and induced the expression of involucrin, which is involved in skin barrier keratinocyte terminal differentiation. In addition, ES0 inhibited protease-activated receptor-2 activation in HaCaT human keratinocytes stimulated by stratum corneum tryptic enzyme and T helper type (Th) 1, Th2, and Th17 cytokine production in Staphylococcal enterotoxin B–stimulated CD4+ lymphocytes. Lastly, ES0 markedly activated innate immunity through toll-like receptor (TLR) 2, TLR4, and TLR5 activation (in recombinant human embryonic kidney 293 cells) and through antimicrobial peptide induction (psoriasin, human beta-defensin-2, and cathelicidin), mainly through TLR5 activation (in normal human keratinocytes).ConclusionOverall, these in vitro results confirm the marked regulatory activity of this A. dolomiae extract on inflammatory and immune responses, which may be of value by virtue of its potential as an adjunctive treatment of AD inflammatory and pruritic lesions.

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Section: Discussionmentioning

confidence: 51%

“…Polymerase chain reaction (PCR) array analysis was conducted as previously described in a model of AD induction in NHK 25,26. Briefly, NHK were stimulated for 24 h with 10 µg/mL polyinosinic/polycytidylic acid (poly I:C) and 3 ng/mL of each cytokine, tumor necrosis factor alpha (TNFα), IL-4, and IL-13 (R&D Systems, Lille, France).…”

Section: Methodsmentioning

confidence: 99%

Anti-inflammatory and immunomodulatory effects of <em>Aquaphilus dolomiae</em> extract on in vitro models

Ariès

Hernandez-Pigeon

Vaissiere

et al. 2016

CCID

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“…For example, NKT cells can suppress immune responses during various conditions such as cancer or UV-induced photo damage. Conversely, NKT cells are also able to activate immune responses, such as in psoriasis and liver inflammation272829. In this paper we demonstrate that other T cell subclasses are not involved in the effector phase of our animal model of EBA.…”

Section: Discussionmentioning

confidence: 64%

T cells mediate autoantibody-induced cutaneous inflammation and blistering in epidermolysis bullosa acquisita

Bieber

Witte

Sun

et al. 2016

Sci Rep

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T cells are key players in autoimmune diseases by supporting the production of autoantibodies. However, their contribution to the effector phase of antibody-mediated autoimmune dermatoses, i.e., tissue injury and inflammation of the skin, has not been investigated. In this paper, we demonstrate that T cells amplify the development of autoantibody-induced tissue injury in a prototypical, organspecific autoimmune disease, namely epidermolysis bullosa acquisita ( T cells are essential regulators of host defense and exhibit direct cytotoxic as well as regulatory properties. The presence or absence of pro-inflammatory compared with regulatory T cell subsets affects the development and outcome of inflammatory reactions. Misbalance of T cell populations leads to autoimmune disorders, including systemic lupus erythematosus (SLE), different autoimmune bullous dermatoses (AIBDs) and rheumatoid arthritis (RA) [1][2][3] . In these diseases, the contribution of T cells to antibody production and maintenance of the autoimmune response has clearly been demonstrated 4,5 . In recent decades, the understanding of autoantibody-induced tissue injury has greatly improved. However, the role of T cells during the effector phase of autoimmune skin blistering diseases, i.e., tissue injury and inflammation in the targeted organs, is not completely understood. In this study, we investigated the role of T cells during this phase, using a mouse model of epidermolysis bullosa acquisita (EBA), a prototypical organ-specific autoimmune disease 6,7 . EBA is caused by autoantibodies directed against type VII collagen (COL7), an integral component of anchoring fibrils 8 . Animal models, employing antibody transfer into mice 9,10 , have added to a greater understanding of the mechanisms leading to blistering in EBA 9,11,12 . Based on the current understanding of EBA pathogenesis, the effector phase of EBA is predominantly driven by neutrophils -their depletion leading to a complete absence of experimental EBA 13. With regard to T cell involvement during this phase, in vivo and in vitro data have been contradictory. In vivo data indicated a T cell-independent process: Transfer of total IgG isolated from rabbits that had been immunized with COL7 into T cell-deficient mice induced subepidermal blistering 9 . However, in that study, no wild-type control for evaluation of the extent of blistering was included. In other

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“…dermal fibroblasts, epidermal keratinocytes, and resident immune cells) through the release of numerous cytokines. In this complex network of interactions, keratinocytes are now considered to play a key role as bona fide innate immune cells, capable of secreting cytokines, chemokines, and antimicrobial peptides in response to various stimuli [3]. Psoriasis has been reported to be a Th1-and Th17-driven pathology [4].…”

Section: Introductionmentioning

confidence: 99%

Oncostatin M overexpression induces skin inflammation but is not required in the mouse model of imiquimod‐induced psoriasis‐like inflammation

et al. 2016

Self Cite

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Oncostatin M (OSM) has been reported to be overexpressed in psoriasis skin lesions and to exert proinflammatory effects in vitro on human keratinocytes. Here, we report the proinflammatory role of OSM in vivo in a mouse model of skin inflammation induced by intradermal injection of murine OSM-encoding adenovirus (AdOSM) and compare with that induced by IL-6 injection. Here, we show that OSM potently regulates the expression of genes involved in skin inflammation and epidermal differentiation in murine primary keratinocytes. In vivo, intradermal injection of AdOSM in mouse ears provoked robust skin inflammation with epidermal thickening and keratinocyte proliferation, while minimal effect was observed after AdIL-6 injection. OSM overexpression in the skin increased the expression of the S100A8/9 antimicrobial peptides, CXCL3, CCL2, CCL5, CCL20, and Th1/Th2 cytokines, in correlation with neutrophil and macrophage infiltration. In contrast, OSM downregulated the expression of epidermal differentiation genes, such as cytokeratin-10 or filaggrin. Collectively, these results support the proinflammatory role of OSM when it is overexpressed in the skin. However, OSM expression was not required in the murine model of psoriasis induced by topical application of imiquimod, as demonstrated by the inflammatory phenotype of OSM-deficient mice or wild-type mice treated with anti-OSM antibodies.Keywords: Imiquimod · Keratinocyte · Oncostatin M · Psoriasis · Skin inflammation Additional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Dr. Jean-François Jégou e-mail: jean-francois.jegou@univ-poitiers.fr IntroductionPsoriasis is the most common inflammatory skin disease affecting 2-3% of the adult population, mainly in developed countries, Eur. J. Immunol. 2016Immunol. . 46: 1737Immunol. -1751 in which patients develop skin lesions characterized by erythematous and scaly plaques [1]. The histological features of psoriatic skins are a thickening of the epidermis resulting from an altered keratinocyte differentiation associated with a hyperplasia at the basement membrane, a hyperkeratosis and a parakeratosis (loss of the granular layer and abnormal presence of cell nuclei in the cornified layer) [1,2]. At the inflammatory site, these alterations of the epidermis are the consequence of a crosstalk between infiltrating immune cells and tissue resident cells (e.g. dermal fibroblasts, epidermal keratinocytes, and resident immune cells) through the release of numerous cytokines. In this complex network of interactions, keratinocytes are now considered to play a key role as bona fide innate immune cells, capable of secreting cytokines, chemokines, and antimicrobial peptides in response to various stimuli [3]. Psoriasis has been reported to be a Th1-and Th17-driven pathology [4]. The IL-23/IL-17 axis plays a crucial role in the pathogenesis of the disease, as demonstrated by the detection of IL-23 producing DCs and the expression of IL-17 and IL-22 by T cells and type 3...

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Keratinocytes under Fire of Proinflammatory Cytokines: Bona Fide Innate Immune Cells Involved in the Physiopathology of Chronic Atopic Dermatitis and Psoriasis

Cited by 89 publications

References 68 publications

Anti-inflammatory and immunomodulatory effects of <em>Aquaphilus dolomiae</em> extract on in vitro models

Anti-inflammatory and immunomodulatory effects of <em>Aquaphilus dolomiae</em> extract on in vitro models

T cells mediate autoantibody-induced cutaneous inflammation and blistering in epidermolysis bullosa acquisita

Oncostatin M overexpression induces skin inflammation but is not required in the mouse model of imiquimod‐induced psoriasis‐like inflammation

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