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IL-17 and psoriasis

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https://www.readbyqxmd.com/read/29150564/essential-role-of-card14-in-murine-experimental-psoriasis
#1
Mayuri Tanaka, Kouji Kobiyama, Tetsuya Honda, Kozue Uchio-Yamada, Yayoi Natsume-Kitatani, Kenji Mizuguchi, Kenji Kabashima, Ken J Ishii
Caspase recruitment domain family member 14 (CARD14) was recently identified as a psoriasis-susceptibility gene, but its immunological role in the pathogenesis of psoriasis in vivo remains unclear. In this study, we examined the role of CARD14 in murine experimental models of psoriasis induced by either imiquimod (IMQ) cream or recombinant IL-23 injection. In all models tested, the psoriasiform skin inflammation was abrogated in Card14(-/-) mice. Comparison of the early gene signature of the skin between IMQ-cream-treated Card14(-/-) mice and Tlr7(-/-)Tlr9(-/-) mice revealed not only their similarity, but also distinct gene sets targeted by IL-23...
November 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29148410/th17-gene-expression-in-psoriatic-arthritis-synovial-fluid-and-peripheral-blood-compared-to-osteoarthritis-and-cutaneous-psoriasis
#2
Fatima Abji, Remy A Pollock, Kun Liang, Vinod Chandran, Dafna D Gladman
OBJECTIVES: The IL-23/IL-17 axis is central to the pathogenesis of psoriatic arthritis (PsA). We aimed to identify Th17 signalling genes that are dysregulated in synovial fluid of PsA compared to osteoarthritis (OA) patients and to determine if differences in peripheral blood can distinguish PsA from psoriasis patients and controls. METHODS: Synovial fluid cells (SFCs) from 14 PsA and 9 OA patients were obtained and stored in TRIzol reagent. RNA was isolated by phenol-chloroform extraction and purified with RNeasy miniprep kits...
November 9, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29144382/treatment-approaches-to-moderate-to-severe-psoriasis
#3
REVIEW
Paolo Gisondi, Micol Del Giglio, Giampiero Girolomoni
Psoriasis is a common disease, which has a considerable impact on patients and the health care system. Treatment approaches to the disease may be various because some issues are not definitely addressed. Moreover, the therapeutic paradigms are continuously changing because of the recent approval of new treatments for psoriasis such as interleukin (IL)-17 inhibitors and apremilast. In this review, the factors influencing psoriasis severity, the indications for systemic treatments, the overall parameters to be considered in the treatment choice, life style interventions, and the recommendations for the use, screening, and monitoring of systemic therapies available including acitretin, cyclosporine, methotrexate, apremilast, adalimumab, etanercept, infliximab, secukinumab, ixekizumab, and ustekinumab are discussed...
November 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29142248/the-psoriasis-associated-il-17a-induces-and-cooperates-with-il-36-cytokines-to-control-keratinocyte-differentiation-and-function
#4
Carolina M Pfaff, Yvonne Marquardt, Katharina Fietkau, Jens M Baron, Bernhard Lüscher
Psoriasis is a TH17-driven inflammatory disease affecting a significant proportion of the world population. The molecular consequences of IL-17 signaling in the skin are only partially understood. Therefore, we evaluated the IL-17A effects on organotypic 3-dimensional skin models and observed that IL-17A interfered with keratinocyte differentiation. In agreement with this phenotype, IL-17A repressed the expression of many genes encoding structural proteins. Moreover, genes encoding anti-microbial peptides were induced, resulting in a strengthening of the chemical barrier...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138056/skin-specific-cd301b-dermal-dendritic-cells-drive-il-17-mediated-psoriasis-like-immune-response-in-mice
#5
Tae-Gyun Kim, Sung Hee Kim, Jeyun Park, Wanho Choi, Moah Sohn, Hye Young Na, Minseok Lee, Jae Won Lee, Soo Min Kim, Do-Young Kim, Hyoung-Pyo Kim, Jae-Hoon Choi, Chae Gyu Park, Min-Geol Lee
Conventional dendritic cells (cDCs) are composed of heterogeneous subsets commonly arising from DC-committed progenitors. A population of CD301b-expressing DCs has recently been identified in non-lymphoid barrier tissues such as skin. However, whether CD301b(+) DCs in the skin represent ontogenetically unique subpopulation of migratory cDCs has not been fully addressed. Here, we demonstrated that CD301b(+) dermal DCs were distinct subpopulation of FLT3L-dependent CD11b(+) cDC2 lineage which required an additional GM-CSF cue for the adequate development...
November 11, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29137840/resolvin-d1-attenuates-imiquimod-induced-mice-psoriasiform-dermatitis-through-mapks-and-nf-%C3%AE%C2%BAb-pathways
#6
Juntao Xu, Xiaoru Duan, Feng Hu, Devesh Poorun, Xinxin Liu, Xin Wang, Song Zhang, Lu Gan, Mengwen He, Ke Zhu, Zhangyin Ming, Hongxiang Chen
BACKGROUND: Resolvin D1 (RvD1), a pro-resolution lipid mediator derived from docosahexaenoic acid (DHA), has been described to promote several kinds of inflammatory resolution. However, the effects and anti-inflammatory mechanisms of RvD1 on psoriasis have not been previously reported. OBJECTIVE: The present study aimed to determine the protective effects and the underlying mechanisms of RvD1 on imiquimod (IMQ)-induced psoriasiform dermatitis. METHODS: Mice were topically treated with IMQ to develop psoriasiform dermatitis on their shaved back, pretreated intraperitoneally (i...
November 11, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29130553/the-akkermansia-muciniphila-is-a-gut-microbiota-signature-in-psoriasis
#7
LiRong Tan, Shuang Zhao, Wu Zhu, Lisha Wu, Jie Li, MinXue Sheng, Li Lei, Xiang Chen, Cong Peng
Psoriasis is an immune-mediated chronic inflammatory skin disease. Although its pathogenesis is not fully understood, Th17 cells and the cytokines they produce, such as IL-17, IL-22 and IL-23, play critical roles in the pathogenesis of psoriasis. Evidence has demonstrated that psoriasis has some common features, including immune responses (due to Th17 cells) and inflammatory cytokine profiles, with systematic diseases including inflammatory bowel diseases (IBDs) and obesity. Recently, studies have demonstrated that the gut microbiota plays a crucial role in host homeostasis and immune response, particular in Th17 cells, but the role of the gut microbiota in psoriasis remains unclear...
November 11, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/29110556/the-impact-of-biologic-agents-on-health-related-quality-of-life-outcomes-in-patients-with-psoriasis
#8
Jillian Frieder, Dario Kivelevitch, Connie Tran Fiore, Saadeddine Saad, Alan Menter
Psoriasis is a common, immune-mediated skin disease often associated with significant physical and psychosocial impairment. Antipsoriatic biologic agents offer patients unparalleled treatment potential in regard to greater skin clearance and overall improved quality of life. Evaluation of the therapeutic efficacy of biologic agents on the full psoriasis disease burden must account for their impact on both physical symptoms, as well as patient-reported, health-related quality of life (HRQoL) measurements. Areas covered: Results from numerous clinical trials demonstrate the significant clinical efficacy of biological agents targeting tumor necrosis factor-α (TNF-α) and the interleukin (IL)-12/23 and IL-17 immune pathways...
November 7, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/29103334/a-systematic-review-of-active-comparator-controlled-clinical-trials-in-patients-with-moderate-to-severe-psoriasis
#9
Daniel J No, Mina Amin, Tina Bhutani, Jashin J Wu
PURPOSE: Interleukin (IL)-17 and IL-23 inhibitors are the newest biologic agents used in the management of moderate-to-severe psoriasis. Active comparator studies allow for direct comparison of different biologic agents. We sought to systematically investigate the efficacy of newer biologic agents compared to earlier biologics. MATERIALS AND METHODS: We conducted a literature search for randomized control trials that compared the efficacy of a biologic agent with an active comparator...
November 6, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29103330/a-new-class-of-therapeutic-biologic-agents-for-combatting-psoriasis-anti-il-23-agents
#10
Annalisa Tonini, Bruno Gualtieri, Salvatore Panduri, Marco Romanelli, Andrea Chiricozzi
Psoriasis is a chronic inflammatory skin disease whose pathogenesis is driven by multiple cytokine-mediated pathways. In this immunologic setting, the centrality of the IL-23/IL-17 axis and its therapeutic relevance has emerged. Areas covered: This review is aimed at collecting preliminary data on IL23p19 blockers developed for the treatment of plaque psoriasis. Three agents, guselkumab, risankizumab, and tildrakizumab, are currently being tested in phase III trials, while LY2525623 is currently being tested in phase II trials...
November 6, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29076381/chronic-mucocutaneous-candidiasis-what-can-we-conclude-about-il-17-antagonism
#11
Kevin Veverka, Steven R Feldman
PURPOSE: IL-17 antagonists are effective for psoriasis in clinical trials, but long-term safety is not fully characterized. Since chronic mucocutaneous candidiasis (CMC) is caused by defects in the IL-17 pathway, CMC risk data has been touted as providing reassurance about the safety of IL-17 antagonism. METHODS: We performed a literature review to identify patients with CMC and compared the prevalence of cancer in these patients to the reported 5-year prevalence...
October 27, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29074858/high-fat-diet-exacerbates-murine-psoriatic-dermatitis-by-increasing-the-number-of-il-17-producing-%C3%AE-%C3%AE-t-cells
#12
Satoshi Nakamizo, Tetsuya Honda, Akimasa Adachi, Takahiro Nagatake, Jun Kunisawa, Akihiko Kitoh, Atsushi Otsuka, Teruki Dainichi, Takashi Nomura, Florent Ginhoux, Koichi Ikuta, Gyohei Egawa, Kenji Kabashima
Psoriasis is a common, chronic inflammatory skin disease characterized by epidermal hyperplasia via the IL-23/IL-17 axis. Various studies have indicated the association between obesity and psoriasis, however, the underlying mechanisms remains unclarified. To this end, we focused on high-fat diet (HFD) in this study, because HFD is suggested as a contributor to obesity, and HFD-fed mice exhibit exacerbated psoriatic dermatitis. Using murine imiquimod (IMQ)-induced psoriasis and HFD-induced obesity models, we have revealed a novel mechanism of HFD-induced exacerbation of psoriatic dermatitis...
October 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29073354/oral-administration-of-vanillin-improves-imiquimod-induced-psoriatic-skin-inflammation-in-mice
#13
Hui-Man Cheng, Feng-Yuan Chen, Chia-Cheng Li, Hsin-Yi Lo, Yi-Fang Liao, Tin-Yun Ho, Chien-Yun Hsiang
Vanillin is one of the most widely used flavoring products worldwide. Psoriasis is a chronic inflammatory skin disorder. The interleukin-23 (IL-23)/interleukin-17 (IL-17) axis plays a critical role in psoriasis. Here, we analyzed the effect of vanillin on imiquimod (IMQ)-induced psoriatic skin inflammation in mice. Mice were treated topically with IMQ on the back skin and orally with various amounts of vanillin for 7 consecutive days. Vanillin significantly improved IMQ-induced histopathological changes of skin in a dose-dependent manner...
November 14, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29058501/review-of-il-17-inhibitors-for-psoriasis
#14
Mina Amin, Kavita Darji, Daniel J No, Tina Bhutani, Jashin J Wu
BACKGROUND: The development of biologic agents directed against distinct cytokines and receptors has advanced the therapeutic options available for psoriasis patients. Evidence from preclinical studies suggests that IL-17 may contribute to the pathogenesis of psoriasis. OBJECTIVE: The objective was to review the safety and efficacy profile for each IL-17 inhibitor by evaluating phase III clinical trial data. METHODS: We reviewed the results of phase III clinical trials for the IL-17 inhibitors secukinumab, ixekizumab, and brodalumab...
October 23, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29046031/-innate-lymphoid-cells-and-their-role-in-immune-response-regulation
#15
Bibiana Patricia Ruiz-Sánchez, David Cruz-Zárate, Iris Estrada-García, Isabel Wong-Baeza
Innate lymphoid cells (ILCs) are lymphocytes lacking antigen recognition receptors and become activated in response to cytokines and through microbe-associated molecular pattern (MAMP) receptors. ILCs are found mainly in mucosal tissues and participate in the immune response against infections and in chronic inflammatory conditions. ILCs are divided in ILC-1, ILC-2 and ILC-3, and these cells have analogue functions to those of immune adaptive response lymphocytes Th1, Th2 and Th17. ILC-1 express T-bet, produce IFNγ, protect against infections with intracellular microorganisms and are related to inflammatory bowel disease immunopathology...
July 2017: Revista Alergia Mexico: Organo Oficial de la Sociedad Mexicana de Alergia e Inmunología, A.C
https://www.readbyqxmd.com/read/29043884/guselkumab-for-psoriasis-a-critical-appraisal-of-phase-iii-studies
#16
Zenas Zn Yiu, Richard B Warren
Biologic therapies have raised the frontiers of accepted treatment efficacy for severe psoriasis. Guselkumab is an IgG1 monoclonal antibody that binds to the p19 subunit and inhibits IL-23. In three Phase III randomized, active comparator and placebo controlled trials, guselkumab demonstrated superior efficacy and a comparable safety profile when assessed against adalimumab and ustekinumab. Critical appraisal highlighted uncertainties over risk of bias from missing details in the trial publications that would be overcome with the provision of accompanying trial protocols, as well as the need for a head-to-head trial against an IL-17 inhibitor...
October 18, 2017: Immunotherapy
https://www.readbyqxmd.com/read/29039484/mir%C3%A2-203-contributes-to-il%C3%A2-17%C3%A2-induced-vegf-secretion-by-targeting-socs3-in-keratinocytes
#17
Yuanyuan Xu, Yongzhi Ji, Xiaoou Lan, Xinghua Gao, Hong-Duo Chen, Long Geng
Interleukin (IL)-17 signaling serves an important role in the development and pathogenesis of psoriasis; a chronic skin disease characterized by increased dermal vascularity and the hyperproliferation of keratinocytes. microRNA (miR)‑203 is preferentially expressed in the skin and is an important regulator of keratinocyte differentiation. miR‑203 has been implicated in a number of skin diseases, including psoriasis. However, the role of miR‑203 in IL‑17‑induced vascular endothelial growth factor (VEGF) secretion has yet to be elucidated...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29021166/an-analysis-of-il-36-signature-genes-and-individuals-with-il1rl2-knockout-mutations-validates-il-36-as-a-psoriasis-therapeutic-target
#18
Satveer K Mahil, Marika Catapano, Paola Di Meglio, Nick Dand, Helena Ahlfors, Ian M Carr, Catherine H Smith, Richard C Trembath, Mark Peakman, John Wright, Francesca D Ciccarelli, Jonathan N Barker, Francesca Capon
Interleukin (IL)-36α, IL-36β, and IL-36γ are innate mediators of acute epithelial inflammation. We sought to demonstrate that these cytokines are also required for the pathogenesis of plaque psoriasis, a common and chronic skin disorder, caused by abnormal T helper 17 (TH17) cell activation. To investigate this possibility, we first defined the genes that are induced by IL-36 cytokines in primary human keratinocytes. This enabled us to demonstrate a significant IL-36 signature among the transcripts that are up-regulated in plaque psoriasis and the susceptibility loci associated with the disease in genome-wide studies...
October 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28983980/three-cases-of-facial-erythema-with-dryness-and-pruritus-in-psoriasis-patients-during-treatment-with-il-17-inhibitors
#19
Tomohiro Oiwa, Tetsuya Honda, Atsushi Otsuka, Kenji Kabashima
The development of psoriasis, a common, chronic inflammatory skin disease, significantly depends on interleukin (IL)-17 (1). Anti-IL-17 inhibitors, such as ixekinumab (anti-IL-17A antibody), secukinumab (anti-IL-17A antibody) and brodalumab (anti-IL-17 receptor A (IL-17RA) antibody) exert excellent therapeutic effects on psoriasis (2). On the other hand, since IL-17 is an important cytokine for preventing fungal infections, skin side effects such as cutaneous candidiasis are occasionally seen during the administration of IL-17 inhibitors (3)...
October 6, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28977706/dust-mite-induces-multiple-polar-t-cell-axes-in-human-skin
#20
Kunal Malik, Benjamin Ungar, Sandra Garcet, Riana Dutt, Daniel Dickstein, Xiuzhong Zheng, Hui Xu, Yeriel D Estrada, Mayte Suárez-Fariñas, Avner Shemer, James G Krueger, Emma Guttman-Yassky
BACKGROUND: House dust mite/HDM atopy patch test/APT elicits positive reactions in a high fraction of atopic dermatitis/AD and healthy individuals. Experimental systems for new-onset/chronic AD are needed to support rapid therapeutic development, particularly since animal models representing human AD are lacking. While HDM APT has been considered to simulate AD, its suitability to model AD's emerging Th2/Th22 phenotype with Th1 and Th17 components is unknown. OBJECTIVE: To assess whether HDM APT reproduces AD...
October 4, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
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