Association between single nucleotide polymorphisms IL17RA rs4819554 and IL17E rs79877597 and Psoriasis in a Spanish cohort.

Batalla, Ana; Coto, Eliécer; González-Lara, Leire; González-Fernández, Daniel; Gómez, Juan; Aranguren, Tamara F.; Queiró, Rubén; Santos‐Juanes, Jorge; López‐Larrea, Carlos; Coto‐Segura, Pablo

doi:10.1016/j.jdermsci.2015.06.011

Cited by 44 publications

(58 citation statements)

References 46 publications

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“…Whether the effects of keratinocyte-derived IL-17E on macrophages is crucial for the recruitment of neutrophils in psoriatic lesions in vivo has to be further investigated. Stressing a possible pathologic role of IL-17E in psoriasis, a single nucleotide polymorphism rs79877597 in the IL17E gene was associated with more severe psoriasis and the presence of psoriatic arthritis (Batalla et al, 2015). Furthermore, skin improvement after phototherapy correlated with a decrease of IL-17E serum levels in one patient presenting high steady-state levels of this cytokine (Otsuka et al, 2012).…”

Section: Accepted Manuscriptmentioning

confidence: 98%

Keratinocyte-Derived IL-17E Contributes to Inflammation in Psoriasis

Senra

Stalder

Martínez

et al. 2016

Journal of Investigative Dermatology

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Psoriasis is a chronic inflammatory skin disorder effectively treated by blocking IL-17RA, a receptor chain used by several IL-17 family members, including IL-17E. Although IL-17A is critically involved in the pathogenesis of psoriasis, the contribution of IL-17E remains unknown. Here we show that IL-17E(+) cells are more abundant than IL-17A(+) cells in lesional psoriatic skin. IL-17E synthesis is increased in keratinocytes within psoriatic plaques, and macrophages having a mixed M1/M2 phenotype represent an important proportion of the IL-17E(+) cells infiltrating the dermis. Mechanistically, macrophages do not synthetize but rather take up IL-17E via receptor-mediated clathrin-dependent endocytosis. Furthermore, monocyte-derived macrophages in vitro polarized in M2, but not M1, express the IL-17E receptor and respond to IL-17E by preferentially producing inflammatory cytokines and chemokines involved in neutrophil recruitment. Remarkably, IL-17E expression in lesional psoriatic skin correlates with the number of neutrophils while being inversely proportional to the number of infiltrating T cells. These data provide strong evidence for a proinflammatory role of keratinocyte-derived IL-17E in psoriasis, possibly via macrophage activation.

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Section: Accepted Manuscriptmentioning

confidence: 98%

Keratinocyte-Derived IL-17E Contributes to Inflammation in Psoriasis

Senra

Stalder

Martínez

et al. 2016

Journal of Investigative Dermatology

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“…In particular, a SNP in the IL17E gene is positively correlated with severe forms of psoriasis in a Spanish cohort of patients [154]. However, the effect of this polymorphism on IL-17E expression and/or function remains unknown.…”

Section: Il-17 Family Cytokines In Host Protection and Inflammationmentioning

confidence: 99%

Interleukin 17 Family Cytokines: Signaling Mechanisms, Biological Activities, and Therapeutic Implications

Monin

Gaffen

2017

Cold Spring Harb Perspect Biol

263

235

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The cytokines of the IL-17 family play a central role in the control of infections, especially extracellular fungi. Conversely, if unrestrained, these inflammatory cytokines contribute to the pathology in numerous autoimmune and chronic inflammatory conditions. Recent advances have led to the approval of IL-17A-blocking biologics for the treatment of moderate to severe plaque psoriasis, but much remains to be understood about the biological functions, regulation and signaling pathways downstream of these factors. In this review, we outline the current knowledge on signal transduction and known physiological activities of IL-17 family cytokines. We will highlight in particular the current understanding of these cytokines in the context of skin manifestations of disease.

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“…The role of IL‐17 in psoriasis determines whether the variation of IL‐17A/IL17RA genes is related to an increased susceptibility to psoriasis and influences the disease severity or the risk for psoriatic arthritis. Batalla et al . identified the IL17RA rs4819554 single nucleotide polymorphisms (SNP) as a risk factor in the Spanish population, moreover mainly among Cw6‐positive patients.…”

Section: The Role Of Interleukin‐17 In Psoriasismentioning

confidence: 99%

Interleukin‐17 as a factor linking the pathogenesis of psoriasis with metabolic disorders

Owczarczyk‐Saczonek

Placek

2016

Int J Dermatology

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Psoriasis is a systemic disease with numerous concomitant metabolic disorders. Apparently, T-helper 17 lymphocytes and interleukin (IL)-17 constitute an important element linking those disorders. The role of IL-17 has been confirmed by numerous studies, although it remains not completely understood, and the study results are controversial. Based on the studies performed so far, it is assumed that IL-17 contributes to development of atherosclerosis by means of: stimulation of production of proinflammatory compounds; induction of apoptosis of endothelial cells and heart muscle cells; stimulation of von Willebrand factor production; and induction of the matrix metalloproteinase-9 (atherosclerotic plaque rupture). On the other hand, IL-17 may exert protective activity due to inhibition of proatherogenic interferon-γ and vascular cell adhesion molecule-1, and production of type I collagen by smooth muscle cells. The role of IL-17 in the pathogenesis of obesity is as important as other proinflammatory cytokines. On the other hand, its deficiency increases diet-induced obesity and accelerates adipose tissue accumulation. Although the role of IL-17A in the pathogenesis of metabolic disorders in humans remains controversial, introduction of anti-IL-17A treatments brings hope that development of metabolic disorders in patients with psoriasis may be inhibited.

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Association between single nucleotide polymorphisms IL17RA rs4819554 and IL17E rs79877597 and Psoriasis in a Spanish cohort.

Cited by 44 publications

References 46 publications

Keratinocyte-Derived IL-17E Contributes to Inflammation in Psoriasis

Keratinocyte-Derived IL-17E Contributes to Inflammation in Psoriasis

Interleukin 17 Family Cytokines: Signaling Mechanisms, Biological Activities, and Therapeutic Implications

Interleukin‐17 as a factor linking the pathogenesis of psoriasis with metabolic disorders

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