Expression of Interferon-Gamma Receptors in Normal and Psoriatic Skin

Scheynius, Annika; Fransson, Jessica; Johansson, Catharina; Hammar, H; Baker, Barbara S.; Fry, Lionel; Valdimarsson, H.

doi:10.1111/1523-1747.ep12556086

Cited by 48 publications

(25 citation statements)

References 26 publications

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“…However, the presence of this receptor in normal and psoriatic skin has been reported in two different studies. 18,19 The results of our study showed that the expression of IFN-R on the tumour cells of BCC was significantly decreased compared with the overlying epidermis and the epidermis of normal skin. The low expression of IFN-R, or a differential defective intracellular signalling of the receptor complex on BCC cells, may account for the reduced responsiveness of these cells to rHuIFN-.…”

Section: Discussionmentioning

confidence: 69%

Expression of interferon-gamma receptors and interferon-gamma-induced up-regulation of intercellular adhesion molecule-1 in basal cell carcinoma; decreased expression of IFN-γR and shedding of ICAM-1 as a means to escape immune surveillance

et al. 1998

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Section: Discussionmentioning

confidence: 69%

Expression of interferon-gamma receptors and interferon-gamma-induced up-regulation of intercellular adhesion molecule-1 in basal cell carcinoma; decreased expression of IFN-γR and shedding of ICAM-1 as a means to escape immune surveillance

et al. 1998

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“…Considering that IFN-is an antiproliferative cytokine and inducer of squamous differentiation, the latter findings represent a paradox. This discrepancy can be due to an intrinsic defect in the response of psoriatic keratinocytes to IFN-, and/or to the altered localization and expression of the IFN-receptor complex in the epidermis of psoriatic compared with healthy skin [93]. Recent interest has focused on IL-22, a Th17-and Th22-derived cytokine linking adaptive immune effectors and epithelial dysregulation in psoriasis.…”

Section: Leukocyte-keratinocyte Interplay In Psoriasismentioning

confidence: 99%

Pathobiology of Chronic Inflammatory Skin Diseases: Interplay Between Keratinocytes and Immune Cells as a Target for Anti-Inflammatory Drugs

Albanesi

Pastore

2010

CDM

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Inflammatory dermatoses encompass an enormous area of dermatopathology. These diseases are triggered and maintained by aberrant responses of the cells of the skin immune system. In the last decade it has become clear that epidermal keratinocytes are highly active immunological cells, with a major control over the acute and the chronic phase of skin inflammation by means of cytokine/chemokine production and surface molecule expression. In their turn, these rather disease-specific events driven by keratinocytes lead to a rich inflammatory infiltrate in the whole skin including the upper layers of the epidermis, and eventually in the aggravation and/or perpetuation of the skin disorder. Recently introduced single molecule-targeted biological drugs are offering the best demonstration that a fine definition of the molecular pathways underlying skin disorders is now necessary to identify the relevant therapeutic targets and finally obtain successful treatment of these diseases. In this review, we will summarize recent progress in our understanding of the immunologic basis of psoriasis, allergic contact dermatitis and atopic dermatitis, with special emphasis on potentially effective targets for novel anti-inflammatory drugs.

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“…Keratinocytes are the key-responding cells to the psoriatic pro-inflammatory and pro-proliferative microenvironment since they bear receptors for key inflammatory cytokines, including IL-17 [12], [34], [35]. Surprisingly, although anti-IL-17 therapies showed astonishing clinical efficacy in improving psoriasis, in vitro studies of cultured monolayer keratinocytes identified a restricted number of genes induced by IL-17 [10], [12].…”

Section: Introductionmentioning

confidence: 99%

IL-17 Induces an Expanded Range of Downstream Genes in Reconstituted Human Epidermis Model

et al. 2014

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BackgroundIL-17 is the defining cytokine of the Th17, Tc17, and γδ T cell populations that plays a critical role in mediating inflammation and autoimmunity. Psoriasis vulgaris is an inflammatory skin disease mediated by Th1 and Th17 cytokines with relevant contributions of IFN-γ, TNF-α, and IL-17. Despite the pivotal role IL-17 plays in psoriasis, and in contrast to the other key mediators involved in the psoriasis cytokine cascade that are capable of inducing broad effects on keratinocytes, IL-17 was demonstrated to regulate the expression of a limited number of genes in monolayer keratinocytes cultured in vitro.Methodology/Principal FindingsGiven the clinical efficacy of anti-IL-17 agents is associated with an impressive reduction in a large set of inflammatory genes, we sought a full-thickness skin model that more closely resemble in vivo epidermal architecture. Using a reconstructed human epidermis (RHE), IL-17 was able to upregulate 419 gene probes and downregulate 216 gene probes. As possible explanation for the increased gene induction in the RHE model is that C/CAAT-enhancer-binding proteins (C/EBP) -β, the transcription factor regulating IL-17-responsive genes, is expressed preferentially in differentiated keratinocytes.Conclusions/SignificanceThe genes identified in IL-17-treated RHE are likely relevant to the IL-17 effects in psoriasis, since ixekizumab (anti-IL-17A agent) strongly suppressed the “RHE” genes in psoriasis patients treated in vivo with this IL-17 antagonist.

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Expression of Interferon-Gamma Receptors in Normal and Psoriatic Skin

Cited by 48 publications

References 26 publications

Expression of interferon-gamma receptors and interferon-gamma-induced up-regulation of intercellular adhesion molecule-1 in basal cell carcinoma; decreased expression of IFN-γR and shedding of ICAM-1 as a means to escape immune surveillance

Expression of interferon-gamma receptors and interferon-gamma-induced up-regulation of intercellular adhesion molecule-1 in basal cell carcinoma; decreased expression of IFN-γR and shedding of ICAM-1 as a means to escape immune surveillance

Pathobiology of Chronic Inflammatory Skin Diseases: Interplay Between Keratinocytes and Immune Cells as a Target for Anti-Inflammatory Drugs

IL-17 Induces an Expanded Range of Downstream Genes in Reconstituted Human Epidermis Model

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