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IL-17 and psoriasis

Andreas Pinter, Dagmar Wilsmann-Theis, Wiebke K Peitsch, Rotraut Mössner
Palmoplantar pustular psoriasis, also termed palmoplantar pustulosis (PPP), is a rare disease affecting the palmoplantar regions characterized by sterile, yellow to brown pustules mostly on erythematous skin. PPP is related to a high burden due to painful, impaired and stigmatizing character. Several isoforms of interleukin (IL) have been implicated in its pathophysiology. Here, we report on four patients with PPP treated with the novel IL-17 receptor A blocker brodalumab, in whom this therapy was not successful or showed moderate improvement combined with adverse events...
February 20, 2019: Journal of Dermatology
Kyoko Ikumi, Mizuyu Odanaka, Hiroaki Shime, Masaki Imai, Satoshi Osaga, Osamu Taguchi, Emi Nishida, Hiroaki Hemmi, Tsuneyasu Kaisho, Akimichi Morita, Sayuri Yamazaki
Chronic low-grade inflammation can cause several metabolic syndromes. Patients with psoriasis, a chronic immunological skin inflammation, often develop diabetes. However, it is not clear to date how psoriasis leads to, or is correlated with, glucose intolerance. Here, we investigate whether psoriasis itself correlates with hyperglycemia in humans and mice. In patients, severity of psoriasis was correlated with high blood glucose levels and treatment of psoriasis by phototherapy improved insulin secretion. Imiquimod (IMQ)-induced systemic and cutaneous inflammation in mice, with features of human psoriasis, also resulted in hyperglycemia...
February 15, 2019: Journal of Investigative Dermatology
Di Long, Yongjian Chen, Haijing Wu, Ming Zhao, Qianjin Lu
Interleukin-21 (IL-21), an autocrine cytokine predominantly produced by follicular helper T (Tfh) and T helper 17 (Th17) cells, has been proven to play an important role in the immune system, for example, by promoting proliferation and the development of Tfh and Th17 cells, balancing helper T cell subsets, inducing B cell generation and differentiation into plasma cells, and enhancing the production of immunoglobulin. These effects are mainly mediated by activation of the JAK/STAT, MAPK and PI3K pathways...
February 14, 2019: Journal of Autoimmunity
Asa B Gudmundsdottir, Asa Brynjolfsdottir, Elin Soffia Olafsdottir, Ingibjorg Hardardottir, Jona Freysdottir
Regular bathing in the Blue Lagoon has beneficial effects on psoriasis. Previously, we showed that exopolysaccharides (EPS-Ca) secreted by Cyanobacterium aponinum, a dominating organism in the Blue Lagoon, increased IL-10 secretion by human dendritic cells (DCs). In addition, co-culturing allogeneic CD4+ T cells with DCs matured in the presence of EPS-Ca increased differentiation of T cells into T regulatory cells at the cost of the disease inducing Th17 cells. In the present study, EPS-Ca increased the proportion of DCs expressing CD141, a surface molecule linked to regulatory DCs, and the CD141+ cells secreted more IL-10 than the CD141- cells...
February 14, 2019: International Immunopharmacology
Zahra Omidian, Rizwan Ahmed, Adebola Giwa, Thomas Donner, Abdel Rahim A Hamad
Interleukin-17 (IL-17) is a potent proinflammatory cytokine that protects a host against fungal and extracellular bacterial infections. On the other hand, excessive or dysregulated production of IL-17 underlines susceptibility to autoimmune disease. Consequently, blocking IL-17 has become an effective strategy for modulating several autoimmune diseases, including multiple sclerosis (MS), psoriasis, and rheumatoid arthritis (RA). Notably, however, IL-17 blockade remains ineffective or even pathogenic against important autoimmune diseases such as inflammatory bowel disease (IBD)...
September 17, 2018: Cellular Immunology
Simona-Roxana Georgescu, Mircea Tampa, Constantin Caruntu, Maria-Isabela Sarbu, Cristina-Iulia Mitran, Madalina-Irina Mitran, Clara Matei, Carolina Constantin, Monica Neagu
Psoriasis vulgaris is a chronic, immune-mediated, inflammatory, polygenic skin disorder affecting approximately 2% of the population. It has a great impact on quality of life; patients often experience depression, anxiety, stigma as well as suicidal behavior. Even though psoriasis is one of the most studied dermatological conditions, the pathogenesis of the disease is still not completely elucidated. The complex interactions between keratinocytes, dendritic cells, T-lymphocytes, neutrophils and mast cells are responsible for the histopathological changes seen in psoriasis...
February 10, 2019: International Journal of Molecular Sciences
Ailin Wang, Jianan Wei, Chuanjian Lu, Haiming Chen, Xiaoqin Zhong, Yue Lu, Leng Li, Haiding Huang, Zhenhua Dai, Ling Han
Psoriasis is a chronic recurrent skin inflammatory disease, and inhibition of inflammation may be an effective means of treating psoriasis. The flavonoid genistein has a clear anti-inflammatory effect. However, the anti-psoriatic effects of genistein and their underlying mechanisms remain unclear. In this study, we investigated the effects of genistein on imiquimod (IMQ)-induced psoriasis-like skin lesions in vivo and explored the mechanisms underlying those effects in vitro. It was found that genistein can significantly improve IMQ-induced pathological scores of cutaneous skin lesions in mice, reduce epidermal thickness, and inhibit the expression of inflammatory factors,including interleukin (IL)-1β, IL-6, tumour necrosis factor-alpha (TNF-α), chemokine ligand 2 (CCL2), IL-17 and IL-23...
February 8, 2019: International Immunopharmacology
Charles W Lynde, Jennifer Beecker, Jan Dutz, Cathy Flanagan, Lyn C Guenther, Wayne Gulliver, Kim Papp, Proton Rahman, Dalton Sholter, Gordon E Searles
BACKGROUND: The treat-to-target (T2T) strategy has become established in several medical specialties as a key guidance to optimal therapeutic decision making. T2T may be effective in the assessment of the biologic class of agents called interleukin (IL)-17 inhibitors, which are emerging as a safe and effective treatment option for autoimmune inflammatory conditions such as plaque psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis (AS). OBJECTIVE: The objective of this article is to use a T2T approach for the evaluation of the effectiveness and safety of IL-17 inhibitors in the management of patients with plaque psoriasis, PsA, and AS...
February 11, 2019: Journal of Cutaneous Medicine and Surgery
Jose U Scher, Alexis Ogdie, Joseph F Merola, Christopher Ritchlin
Psoriasis is one of the most common chronic inflammatory skin diseases, affecting 3% of the world's population, and approximately one-third of patients with psoriasis will eventually transition to having psoriatic arthritis (PsA). The evolution from cutaneous to synovio-entheseal inflammation in these patients presents an opportunity to investigate the critical events linked to arthritis development. The events responsible for progression to PsA are currently unclear. Genetic and clinical-demographic risk factors (most notably familial aggregation and psoriasis sub-phenotypes) provide relevant insights into the variables that promote transition...
February 11, 2019: Nature Reviews. Rheumatology
Xue-Li Niu, Yu Huang, Ya-Li Gao, Yu-Zhe Sun, Yang Han, Hong-Duo Chen, Xing-Hua Gao, Rui-Qun Qi
BACKGROUND: As a potent pro-inflammatory cytokine of the interleukin (IL)-1 family, IL-18 was elevated in early active and progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index (PASI). Although results from previous studies have established that IL-18 may aggravate psoriatic inflammation, the mechanisms of this process remain unknown. In this study, IL-18 knock out (KO) mice and Wild-type (WT) mice were used to investigate the effects of IL-18 within a mouse model of psoriasis...
February 5, 2019: Chinese Medical Journal
Luisa Senra, Alessio Mylonas, Ruairi D Kavanagh, Padraic G Fallon, Curdin Conrad, Julia Borowczyk-Michalowska, Ludovic Jean Wrobel, Guerkan Kaya, Nikhil Yawalkar, Wolf-Henning Boehncke, Nicolo Costantino Brembilla
IL-17E (IL-25) is a member of the IL-17 cytokine family involved in the promotion of type 2 immune responses. Recently, IL-17E has been reported to be upregulated in distinct skin inflammatory diseases such as psoriasis, atopic and contact dermatitis. We assessed the role played by IL-17E in skin inflammation. Here we show that IL-17E induces skin inflammation in vivo, characterized by the expression of innate immune response genes and the recruitment of innate immune cells, particularly neutrophils. Genetic deletion or IL-17E neutralization ameliorated skin inflammation induced by imiquimod application, or tape-stripping, with reductions in neutrophil and macrophage infiltration as assessed by t-SNE-guided multiparameter flow cytometry analysis, in mice...
February 6, 2019: Journal of Investigative Dermatology
C Dressler, L Eisert, P A Pham Thi, A Nast
Twenty percent of patients with plaque psoriasis also have psoriatic arthritis - a disease affecting joints and entheses. Different treatment options exist but currently no succinct systematic overview exists. A systematic review of approved systemic treatments for psoriatic arthritis was conducted. We systematically searched in 3 databases (last update 09/2017). Data was extracted for ACR 20/50, HAQ-DI, SF-36 and adverse/serious adverse events after 16-24 weeks. We assessed the quality of evidence using GRADE...
February 8, 2019: Journal of the European Academy of Dermatology and Venereology: JEADV
Elisa Storelli, Niccolò Cassina, Emanuela Rasini, Franca Marino, Marco Cosentino
Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons, appearance of Lewy bodies and presence of neuroinflammation. No treatments currently exist to prevent PD or delay its progression, and dopaminergic substitution treatments just relieve the consequences of dopaminergic neuron loss. Increasing evidence points to peripheral T lymphocytes as key players in PD, and recently there has been growing interest into the specific role of T helper (Th) 17 lymphocytes...
2019: Frontiers in Neurology
Honda Tetsuya, Kabashima Kenji
Lipid mediators, such as prostanoids and leukotrienes (LTs), exert a range of actions through their own receptors on cell surfaces in various pathophysiological conditions. It has been reported that the production of prostanoids and LTs is significantly elevated in the skin lesions of some chronic inflammatory skin diseases, such as atopic dermatitis (AD) and psoriasis, showing the possible involvement of these lipid mediators in the development of those diseases. Although the actual significance of these lipid mediators in humans is still unclear, the findings from studies in mice suggest diverse roles of the lipid mediators in the progression or regulation of these diseases...
February 3, 2019: International Immunology
Giovanni Damiani, Abdulla Watad, Charlie Bridgewood, Paolo Daniele Maria Pigatto, Alessia Pacifico, Piergiorgio Malagoli, Nicola Luigi Bragazzi, Mohammad Adawi
Fasting during the month of Ramadan consists of alternate abstinence and re-feeding periods (circadian or intermittent fasting). Nothing is currently known on the impact of this kind of fasting on psoriasis. A sample of 108 moderate-to-severe plaque psoriasis patients (aged 42.84 ± 13.61 years, 62 males, 46 females) volunteered to take part in the study. A significant decrease in the "Psoriasis Area and Severity Index" (PASI) score after the Ramadan fasting (mean difference = -0.89 ± 1.21, p < 0...
January 27, 2019: Nutrients
Sonja Moos, Alma N Mohebiany, Ari Waisman, Florian C Kurschus
Pathology of psoriasis strongly depends on IL-17A. Monoclonal antibodies blocking either the cytokine or its receptor are amongst the most efficient treatments for psoriatic patients. Keratinocytes can be activated upon exposure to IL-17A and TNFα and secrete secondary cytokines and chemokines in the inflamed skin. In psoriasis and its imiquimod (IMQ)-induced mouse model, a strong skin-infiltration of neutrophils and inflammatory monocytes can be observed. But it is not clear to date how exactly those cellular populations are attracted to the skin and what their contribution to the pathogenesis of the disease is...
January 23, 2019: Journal of Investigative Dermatology
Anna-Karin Ekman, Cecilia Bivik Eding, Ingemar Rundquist, Charlotta Enerbäck
Psoriasis is an inflammatory skin disorder characterized by the hyperproliferation of basal epidermal cells. It is regarded as T-cell mediated, but the role of keratinocytes (KCs) in the disease pathogenesis has reemerged with genetic studies identifying KC-associated genes. We applied flow cytometry on KCs from lesional and non-lesional epidermis to characterize the phenotype in the germinative compartment in psoriasis and observed an overall increase in the stemness markers CD29 (2.4 fold), CD44 (2.9 fold), CD49f (2...
January 23, 2019: Journal of Investigative Dermatology
Beatriz Germán, Ruicheng Wei, Pierre Hener, Christina Martins, Tao Ye, Cornelia Gottwick, Jianying Yang, Julien Seneschal, Katia Boniface, Mei Li
Psoriasis is one of the most common skin inflammatory diseases worldwide. The vitamin D3 analog calcipotriol has been used alone or in combination with corticosteroids in treating plaque psoriasis, but how it suppresses psoriatic inflammation has not been fully understood. Using an experimental mouse psoriasis model, we show that topical calcipotriol inhibited the pivotal IL-23/IL-17 axis and neutrophil infiltration in psoriatic skin, and interestingly, such effects were mediated through the vitamin D receptor (VDR) in keratinocytes (KCs)...
January 24, 2019: JCI Insight
Amy S Paller
Despite extensive discovery about the mutations underlying genetic skin disorders, there have been few therapeutic advances. Better understanding of the molecular changes that may lead to the phenotypic manifestations of genetic disorders may lead to the discovery of new pharmacologic interventions. The ichthyoses are characterized by scaling, inflammation, and an impaired epidermal barrier. Recent studies have uncovered T helper type 17 skewing in ichthyotic skin, resembling psoriasis, and high frequencies of IL-17- and IL-22-expressing T cells in blood, correlating with severity and transepidermal water loss...
January 19, 2019: Journal of Investigative Dermatology
Erica B Lee, Deeti J Pithadia, Kelly A Reynolds, Jashin J Wu
The Institute of Clinical and Economic Review (ICER) issued an updated report regarding the clinical efficacy, value, and budget impact of various psoriasis immunomodulators in August 2018. Specifically, the update included information on two new biologics, guselkumab and certolizumab in the context of their relative cost-effectiveness. Using analyses based on sequential implementation of specific first- and second-line therapies, the ICER found that initiating biologic therapy with an IL-17 inhibitor or guselkumab results in the most clinical improvement, but is also associated with higher costs...
January 22, 2019: Journal of Dermatological Treatment
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