Psoriasis

Perera, Gayathri; Meglio, Paola Di; Nestle, Frank O.

doi:10.1146/annurev-pathol-011811-132448

Cited by 450 publications

(489 citation statements)

References 269 publications

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“…Of note, IL 17 has been shown to induce the secretion of pro inflammatory cytokines (IL 1 and IL 6), antimicrobial pep tides, and several chemokines including IL 8 and CCL20 in human keratinocytes. In addition, the induction of CCL20 by keratinocytes has been suggested as a mechanism that maintains Th17 cells in skin (Perera et al, 2012). We have also found increased expression of Defb4, Cxcl1, S100a7, S100a8, and S100a9 in Tg KLK5 skin, which are genes known to be induced by Il 17 and Il 22.…”

Section: Discussionsupporting

confidence: 59%

Transgenic kallikrein 5 mice reproduce major cutaneous and systemic hallmarks of Netherton syndrome

Furio¹,

Veer²,

Jaillet³

et al. 2014

J Cell Biol

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Section: Discussionsupporting

confidence: 59%

Transgenic kallikrein 5 mice reproduce major cutaneous and systemic hallmarks of Netherton syndrome

Furio¹,

Veer²,

Jaillet³

et al. 2014

J Cell Biol

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“…However, this corresponds with a previous study stating that psoriatic KC lack intrinsic aberrant expression of IL-23, and therefore, IL-23 may not be further reduced by IL-4 in culture conditions (52). In addition, IL-1b and IL-6 are necessary for Th17 induction by DC (6,10). Because of the early inhibition of IL-1b and IL-6 by IL-4, likely DC are not activated and new IL-12 and IL-23 production and the consequent Th17 differentiation are inhibited.…”

Section: Discussionsupporting

confidence: 91%

“…The current concept is that psoriatic plaques (PP) arise as the result of interplay between inflammatory cells and genetically predisposed keratinocytes (KC) (1)(2)(3)(4). Expression levels of antimicrobial peptides are highly upregulated in (non)lesional psoriatic skin, and they are considered to play a role in the induction of psoriasis via immune-modulation such as recruitment of leukocytes (5,6). The activated epidermis is characterized by a high keratin 17 (K17) and a low GATA3 expression, high levels of antimicrobial peptides such as psoriasin (S100A7) and b-defensin-2 (hBD2), growth factors including nerve growth factor (NGF), and the proinflammatory cytokines IL-1b and IL-6 (2,(7)(8)(9).…”

mentioning

confidence: 99%

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IL-4 Downregulates IL-1β and IL-6 and Induces GATA3 in Psoriatic Epidermal Cells: Route of Action of a Th2 Cytokine

Onderdijk

Baerveldt

Kurek

et al. 2015

The Journal of Immunology

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Clinical improvement of psoriasis induced by IL-4 treatment has been ascribed to changes in dermal inflammatory cells, such as activation of Th2 cells and tolerization of dendritic cells by suppressing IL-23 production. The pathologic epidermal alterations in psoriatic lesional skin include increased epidermal expression of IL-1β, IL-6, S100A7, and human β-defensin 2 (hBD2) and a downregulated expression of the epidermal transcription factor GATA3. Effects of IL-4 on the epidermal compartment of psoriasis lesions were not previously investigated. Therefore, we investigated whether IL-4 directly affects abovementioned psoriatic markers in the epidermal compartment. We cultured freshly isolated psoriatic epidermal cells, whole psoriatic and healthy skin biopsies, human keratinocytes and Langerhans cells with IL-4. The secretion of IL-1β and IL-6 by psoriatic epidermal cells was inhibited by IL-4 via transcriptional and posttranscriptional mechanisms, respectively. In normal skin, IL-4 inhibited IL-1β- and IL-17A–induced hBD2 expression in vitro. In addition, IL-4 reduced the protein expression of hBD2 in psoriatic skin biopsies and induced phospho-STAT6 protein. Epidermal GATA3 mRNA and protein were significantly upregulated by IL-4 in epidermal cells and keratinocytes. Our data argue that IL-4 improves psoriasis not only via modification/induction of Th2 cells and type II dendritic cells, but also via direct inhibition of inflammatory cytokines in resident IL-4R–expressing epidermal cells and thereby alters the psoriatic skin phenotype toward a healthy skin phenotype.

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“…Genetic components of the immune system and the epidermis play a role, along with environmental factors that trigger or exacerbate the symptoms of the disease. Psoriasis can have a negative impact on a patient's physical and mental well being and correlates with inconsistent response to therapy, resulting in unsuccessful clinical treatments (Perera et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Computational Systems Biology of Psoriasis: Are We Ready for the Age of Omics and Systems Biomarkers?

Sevimoglu

Arğa

2015

OMICS: A Journal of Integrative Biology

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Computational biology and 'omics' systems sciences are greatly impacting research on common diseases such as cancer. By contrast, dermatology covering an array of skin diseases with high prevalence in society, has received relatively less attention from 'omics' and computational biosciences. We are focusing on psoriasis, a common and debilitating autoimmune disease involving skin and joints. Using computational systems biology and reconstruction, topological, modular, and a novel correlational analyses (based on fold changes) of biological and transcriptional regulatory networks, we analyzed and integrated data from a total of twelve studies from the Gene Expression Omnibus (sample size = 534). Samples represented a comprehensive continuum from lesional and nonlesional skin, as well as bone marrow and dermal mesenchymal stem cells. We identified and propose here a JAK/STAT signaling pathway significant for psoriasis. Importantly, cytokines, interferon-stimulated genes, antimicrobial peptides, among other proteins, were involved in intrinsic parts of the proposed pathway. Several biomarker and therapeutic candidates such as SUB1 are discussed for future experimental studies. The integrative systems biology approach presented here illustrates a comprehensive perspective on the molecular basis of psoriasis. This also attests to the promise of systems biology research in skin diseases, with psoriasis as a systemic component. The present study reports, to the best of our knowledge, the largest set of microarray datasets on psoriasis, to offer new insights into the disease mechanisms with a proposal of a disease pathway. We call for greater computational systems biology research and analyses in dermatology and skin diseases in general.

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Psoriasis

Cited by 450 publications

References 269 publications

Transgenic kallikrein 5 mice reproduce major cutaneous and systemic hallmarks of Netherton syndrome

Transgenic kallikrein 5 mice reproduce major cutaneous and systemic hallmarks of Netherton syndrome

IL-4 Downregulates IL-1β and IL-6 and Induces GATA3 in Psoriatic Epidermal Cells: Route of Action of a Th2 Cytokine

Computational Systems Biology of Psoriasis: Are We Ready for the Age of Omics and Systems Biomarkers?

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