Psoriasis

Meglio, Paola Di; Villanova, Federica; Nestle, Frank O.

doi:10.1101/cshperspect.a015354

Cited by 267 publications

(230 citation statements)

References 180 publications

(227 reference statements)

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“…A compelling and recent example is provided by a study in which nociceptors were shown to modulate the phenotype of dermal DCs in a mouse model of psoriasis 73 . Psoriasis is an immune-mediated inflammatory disease of the skin characterized by epidermal hyperplasia and immune infiltration, in which both innate and adaptive immune cells are thought to have a crucial role 146 . Psoriasis can be modelled in rodents by repeated topical application of imiquimod, a potent immune activator, which leads to the formation of skin lesions resembling human psoriasis 147,148 .…”

Section: Modulated Effects Refsmentioning

confidence: 99%

Crosstalk between the nociceptive and immune systems in host defence and disease

2015

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Nociceptors and immune cells both protect the host from potential threats to homeostasis. There is growing evidence for bidirectional signalling between these two systems, and the underlying mechanisms are beginning to be elucidated. An understanding is emerging of how both the adaptive and innate immune systems can activate and sensitize nociceptors, and, reciprocally, how nociceptors modulate immune cells. In this Review, we discuss how these interactions can be adaptive and useful to the organism but also consider when such signalling might be maladaptive and pathophysiological, contributing to immune-mediated diseases and persistent pain states.

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Section: Modulated Effects Refsmentioning

confidence: 99%

Crosstalk between the nociceptive and immune systems in host defence and disease

2015

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“…One of the best-characterized psoriasis initiation mechanisms is the antimicrobial peptide LL-37-DNA/RNA complex resulted from infection or physical trauma (Di Meglio et al, 2014), which induces inflammation, but how to initiate and develop psoriasis remains unknown. As illustrated in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Two closely related G protein-coupled receptors (PKR1 and PKR2)mediate signal transduction of PKs (Negri et al, 2004, Shojaei et al, 2008). Psoriasis, a chronic cutaneous disorder with a spectrum of clinical phenotypes including red, scaly and well-demarcated skin lesions formed by hyperproliferation of epidermal keratinocytes (KC), affects approximately 1–3% of the worldwide population (Baliwag et al, 2015, Di Meglio et al, 2014, Gottlieb, 2005, Nestle et al, 2009). Besides causing ecological burdens, psoriasis produces a severe psychosocial burden such as anxiety, depression, and perceived stress, therefore significantly impairs the quality of patients' life (Gupta et al, 2015, Tohid et al, 2016, Villasenor-Park et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Numerous inflammatory cytokines, such as IL-17, TNF-а and IL-23, are over-produced in psoriatic skin, with their levels correlated with the severity of psoriasis disease (Baliwag et al, 2015, Kofoed et al, 2015). To target these cytokines in psoriatic disease, some anti-cytokine biologic drugs are emerging (Di Meglio et al, 2014; Eberle et al, 2016). However, as disease biomarkers, none of these cytokines has so far met the sensitivity, specificity, and accuracy criteria that would allow their translation into clinical use (Villanova et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Prokineticin 2 Plays a Pivotal Role in Psoriasis

Shen

et al. 2016

EBioMedicine

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Psoriasis is histologically characterized by keratinocytes (KC) hyperproliferation, inflammation, and increased angiogenesis, but the pathological factor responsible for these symptoms is unknown. Here, a neuroendocrine peptide (prokineticin 2, PK2), is highly expressed in human and mouse psoriatic skins but no significant change in other autoimmune diseases, suggesting that PK2 is a psoriasis-specific factor. Bacterial products significantly up-regulated PK2, implying that infection induces PK2 over-expression. PK2 promoted KC and macrophage to produce interleukin-1 (IL-1), the central player of inflammation and psoriasis, which acts on adjacent fibroblast to induce inflammatory cascades and KC hyperproliferation. IL-1 feeds back on macrophages to induce PK2 production to perpetuate PK2-IL-1 positive feedback loop. PK2 also promoted angiogenesis, another psoriatic symptom. In mouse models, PK2 over-expression aggravated psoriasis while its knock-down inhibited pathological development. The results indicate that PK2 over-production perpetuates psoriatic symptoms by creating PK-2-IL-1 vicious loop. PK2 is a central player in psoriasis and a promising psoriasis-specific target.

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“…Psoriasis is a chronic inflammatory skin disease characterized by increased infiltration of IFNγ-producing Th1 cells as well as IL-17A-producing Th17 cells in the lesional plaques [26]. A model of psoriasis initiation involving the antimicrobial peptide LL-37 and IFNα has been suggested [27,28].…”

Section: Discussionmentioning

confidence: 99%

344 STAT2 is involved in the pathogenesis of psoriasis by promoting CXCL11 and CCL5 production by keratinocytes

Johansen

Hald

Bertelsen

et al. 2016

Journal of Investigative Dermatology

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The JAK/STAT signaling pathway is suggested to play an important role in the pathogenesis of psoriasis, and recently JAK/STAT inhibitors have shown promising results in psoriasis treatment. The present study aimed to characterize the role of STAT2 in psoriasis. We demonstrated an increased expression of STAT2 and an increased level of phosphorylated/activated STAT2 in lesional compared with nonlesional psoriatic skin. Gene silencing of STAT2 by siRNA in human keratinocytes revealed that upon IFNα stimulation CXCL11 and CCL5 were the only two cytokines, among 102 analyzed, found to be regulated through a STAT2-dependent mechanism. Moreover, the regulation of CXCL11 and CCL5 depended on IRF9, but not on STAT1 and STAT6. The CXCL11 and CCL5 expression was increased in lesional compared with nonlesional psoriatic skin, and analysis demonstrated positive correlation between the expression of CXCL11 and IFNγ and between the expression of CCL5 and IFNγ in lesional psoriatic skin. In contrast, no correlation between the expression of CXCL11 and IL-17A and the expression of CCL5 and IL-17A in lesional psoriatic skin was found. Our data suggest that STAT2 plays a role in the psoriasis pathogenesis by regulating the expression of CXCL11 and CCL5, and thereby attracting IFNγ-producing immune cells to the skin.

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Psoriasis

Cited by 267 publications

References 180 publications

Crosstalk between the nociceptive and immune systems in host defence and disease

Crosstalk between the nociceptive and immune systems in host defence and disease

Prokineticin 2 Plays a Pivotal Role in Psoriasis

344 STAT2 is involved in the pathogenesis of psoriasis by promoting CXCL11 and CCL5 production by keratinocytes

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