Psoriasis Pathogenesis: Keratinocytes Are Back in the Spotlight

Garzorz‐Stark, Natalie; Eyerich, Kilian

doi:10.1016/j.jid.2019.01.026

Cited by 38 publications

(32 citation statements)

References 12 publications

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“…in keratinocytes were largely protected from the inflammatory response. 66,67 All these data demonstrate that keratinocytes act as an executor in response to immune cells for developing the full-blown psoriasiform phenotype and maintaining the pathology of psoriasis.…”

Section: Keratinocytes Act As An Executor Of the Inflammatory Circuitmentioning

confidence: 93%

Keratinocyte: A trigger or an executor of psoriasis?

Lai

2020

Journal of Leukocyte Biology

159

108

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Psoriasis is a common chronic inflammatory skin disease characterized by abnormal proliferation/differentiation of keratinocytes and excessive immune cell infiltration in the dermis and epidermis. Over the past 2 decades, immune cells have been considered as the main driver of psoriasis because the neutralizing antibodies targeting the IL-23/IL-17 axis that regulates cross-talk between dendritic cells and T cells achieve tremendous success in the treatment of psoriasis. However, whether keratinocyte would be a driver of psoriasis or just an executor in response to immune cells is still under debate. In this review, we focus on the recent advances in the identification of keratinocyte as a trigger of psoriasis, summarize on the role of keratinocytes in self-perpetuating loop to maintain inflammation in psoriasis, and then discuss the possible roles of keratinocytes in the relapse of psoriasis.

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Section: Keratinocytes Act As An Executor Of the Inflammatory Circuitmentioning

confidence: 93%

Keratinocyte: A trigger or an executor of psoriasis?

Lai

2020

Journal of Leukocyte Biology

159

108

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“…IL-17A and IL-17F are significantly implicated in immune responses to infectious pathogens and in the pathogenesis of inflammatory autoimmune diseases like psoriasis. Furthermore, evidence indicates an additional proinflammatory activity of IL-17C and IL-17E within the pathogenesis of psoriasis (18)(19)(20)(21).…”

Section: Biology Of Il-17a and Il-17fmentioning

confidence: 99%

IL-17A in Psoriasis and Beyond: Cardiovascular and Metabolic Implications

et al. 2020

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Interleukin 17A (IL-17A) is one of the currently known six members of the IL-17 cytokine family and is implicated in immune responses to infectious pathogens and in the pathogenesis of inflammatory autoimmune diseases like psoriasis. Psoriatic skin is characterized by high expression of IL-17A and IL-17F, which act on immune and non-immune cell types and strongly contribute to tissue inflammation. In psoriatic lesions, IL-17A, IL-17E, and IL-17F are involved in neutrophil accumulation, followed by the formation of epidermal micro abscesses. IL-17A together with other Th17 cytokines also upregulates the production of several chemokines that are implicated in psoriasis pathogenesis. IL17A-targeting antibodies show an impressive clinical efficacy in patients with psoriasis. Studies have reported an improvement of at least 75% as measured by the psoriasis area and severity index (PASI) in >80% of patients treated with anti-IL-17A therapy. Psoriasis skin manifestations, cardiovascular as well as metabolic disease in psoriasis appear to share pathogenic mechanisms evolving around IL-17A and its proinflammatory role. Thus, anti-IL-17A therapy not only improves skin manifestations of psoriasis, but also cardiovascular inflammation as well as metabolic factors and different domains of psoriatic arthritis (PsA) including peripheral arthritis, enthesitis, dactylitis, and axial involvement. This review summarizes the biological role of IL-17A, before reviewing currently available data on its role in the physiology and pathophysiology of the skin, as well as the cardiovascular and the metabolic system. In conclusion, clinical recommendations for patients with moderate to severe psoriasis based on the current available data are given.

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“…Rag2-deficient JunB/c-Jun double-mutant mice showed epidermal thickening, altered keratinocyte differentiation, vascular dilatation and slight epidermal abscesses [ 56 ]. The debate over whether abnormalities in the keratinocytes or of the immune system are responsible for triggering the disease is still emerging, suggesting a dynamic contribution of keratinocytes to the pathogenesis [ 45 , 46 , 57 , 58 ].…”

Section: Implication Of Keratinocytesmentioning

confidence: 99%

Transcriptome Profiling Analyses in Psoriasis: A Dynamic Contribution of Keratinocytes to the Pathogenesis

Rioux

Ridha

Simard

et al. 2020

Genes

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Psoriasis is an immune-mediated inflammatory skin disease with a complex etiology involving environmental and genetic factors. A better insight into related genomic alteration helps design precise therapies leading to better treatment outcome. Gene expression in psoriasis can provide relevant information about the altered expression of mRNA transcripts, thus giving new insights into the disease onset. Techniques for transcriptome analyses, such as microarray and RNA sequencing (RNA-seq), are relevant tools for the discovery of new biomarkers as well as new therapeutic targets. This review summarizes the findings related to the contribution of keratinocytes in the pathogenesis of psoriasis by an in-depth review of studies that have examined psoriatic transcriptomes in the past years. It also provides valuable information on reconstructed 3D psoriatic skin models using cells isolated from psoriatic patients for transcriptomic studies.

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Psoriasis Pathogenesis: Keratinocytes Are Back in the Spotlight

Cited by 38 publications

References 12 publications

Keratinocyte: A trigger or an executor of psoriasis?

Keratinocyte: A trigger or an executor of psoriasis?

IL-17A in Psoriasis and Beyond: Cardiovascular and Metabolic Implications

Transcriptome Profiling Analyses in Psoriasis: A Dynamic Contribution of Keratinocytes to the Pathogenesis

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