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Il-23 and psoriasis

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https://www.readbyqxmd.com/read/29226422/pathogenesis-of-psoriasis-and-development-of-treatment
#1
REVIEW
Eisaku Ogawa, Yuki Sato, Akane Minagawa, Ryuhei Okuyama
The pathogenesis of psoriasis can be explained by dysregulation of immunological cell function as well as keratinocyte proliferation/differentiation. Recently, the immunological pathomechanism has been clarified substantially. Whereas T-helper (Th)1 overactivation was thought to induce occurrence of psoriasis, it has been demonstrated that Th17 cells play a key role. Th17 development is maintained by interleukin (IL)-23 mainly produced by dendritic cells. Th17 cells produce various cytokines, including IL-17A, IL-17F and IL-22...
December 10, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/29222947/safety-and-efficacy-of-guselkumab-in-japanese-patients-with-moderate-to-severe-plaque-psoriasis-a-randomised-placebo-controlled-ascending-dose-study
#2
O Nemoto, K Hirose, S Shibata, K Li, H Kubo
BACKGROUND: The Interlukin-23 (IL-23)/Interlukin-17 (IL-17) pathway is central in the pathogenesis of psoriasis. The favourable efficacy and safety of guselkumab, an IL-23 specific monoclonal antibody, has been demonstrated in global Phase 3 studies of plaque psoriasis. OBJECTIVES: To evaluate the safety, efficacy and pharmacokinetics of a single-dose subcutaneous guselkumab in Japanese patients with moderate-to-severe plaque psoriasis. METHODS: Patients with ≥ 10% of total body surface area (BSA) involvement and a Psoriasis Area and Severity Index (PASI) ≥12 were randomised (5:1) to receive guselkumab or placebo in 4 cohorts of this double-blind, placebo-controlled, single ascending dose, single-centre study...
December 9, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29222824/elevated-levels-of-the-antimicrobial-peptide-ll-37-in-hidradenitis-suppurativa-are-associated-with-a-th1-th17-immune-response
#3
R Thomi, C Schlapbach, N Yawalkar, D Simon, D Yerly, R E Hunger
Hidradenitis suppurativa (HS) is an inflammatory skin disease with poorly understood immunopathogenic mechanisms. LL-37 is an antimicrobial peptide, which is transcribed from the CAMP (cathelicidin antimicrobial peptide) gene. Previous reports showed upregulated levels of CAMP and LL-37 in HS lesions and therefore the aim of this study was to compare levels of LL-37 in HS to other inflammatory skin diseases and to establish immunomodulatory functions of LL-37 in HS. We confirm an upregulation of the LL-37 peptide in lesional HS skin with comparable levels as in psoriasis patients and are able to positively correlate the presence of LL-37 in HS with the presence of T cells, macrophages, neutrophils, IFNγ, IL-17, IL-23, TNFα, IL-32 and IL-1β...
December 8, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/29220875/interleukin-21-receptor-signaling-is-not-critically-required-for-imiquimod-induced-psoriasiform-dermatitis-in-mice
#4
Hee Joo Kim, Sung Hee Kim, Tae-Gyun Kim, Je Yun Park, Minseok Lee, Dae Suk Kim, Min-Geol Lee
Psoriasis is largely mediated by interleukin (IL)-23/ T helper (Th) 17 axis, and IL-21 is a pleiotropic cytokine expressed by Th17 cells. Despite previously reported possible pathogenic roles of IL-21 in human psoriasis, we found that IL-21 receptor (IL-21R) signaling was not crucial for imiquimod-induced psoriatic inflammation, using IL-21R-/- mice. The severity of imiquimod-induced psoriatic manifestation and pro-inflammatory Th17 cytokine levels, IL-17A-producing γδ T cells and CD4+ T cells, and in vitro IL-17A production by γδ T cells after IL-23 stimulation was comparable between wild-type and IL-21R-/- mice...
December 8, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/29203226/innately-versatile-%C3%AE-%C3%AE-17%C3%A2-t-cells-in-inflammatory-and-autoimmune-diseases
#5
REVIEW
Pedro H Papotto, Annika Reinhardt, Immo Prinz, Bruno Silva-Santos
IL-17-producing γδ (γδ17) T cells form a versatile subset of cells that respond rapidly to innate stimuli and support the pro-inflammatory functions of different myeloid and lymphoid lineages, being particularly critical in the early stages of inflammatory and autoimmune responses. In mice, under homeostatic conditions, these innate-like lymphocytes are pre-programmed in the fetal thymus, through an intricate process involving both T cell receptor-dependent and -independent signals, which allows them to readily produce IL-17 upon stimulation...
December 1, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29150564/essential-role-of-card14-in-murine-experimental-psoriasis
#6
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
#7
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/29143230/the-efficacy-of-biologic-therapy-for-the-management-of-palmoplantar-psoriasis-and-palmoplantar-pustulosis-a-systematic-review
#8
REVIEW
Isabelle M Sanchez, Eric Sorenson, Ethan Levin, Wilson Liao
INTRODUCTION: Palmoplantar psoriasis (PP) and palmoplantar pustulosis (PPP) are diseases affecting the hands and/or feet that can cause marked physical discomfort and functional disability. The tumor necrosis factor-alpha antagonists adalimumab, etanercept, and infliximab, the interleukin (IL)-17A inhibitors ixekizumab and secukinumab, and the IL-23 or IL-12/IL-23 inhibitors guselkumab and ustekinumab have been well studied for the treatment of moderate to severe plaque psoriasis. Less is known about the efficacy and safety of these agents for the treatment of PP (hyperkeratotic and pustular forms) and PPP...
December 2017: Dermatology and Therapy
https://www.readbyqxmd.com/read/29138056/skin-specific-cd301b-dermal-dendritic-cells-drive-il-17-mediated-psoriasis-like-immune-response-in-mice
#9
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
#10
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
#11
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/29116597/response-to-tetanus-and-pneumococcal-vaccination-following-administration-of-ixekizumab-in-healthy-participants
#12
Elisa V Gomez, Jessie L Bishop, Kimberley Jackson, Talia M Muram, Diane Phillips
BACKGROUND: Ixekizumab (IXE) is an interleukin (IL)-17A antagonist approved for the treatment of adults with moderate-to-severe psoriasis. OBJECTIVE: The objective of this study was to determine if the immune response to tetanus and pneumococcal vaccines in healthy subjects administered IXE was noninferior to control. METHODS: In a randomized, open-label, parallel-group study, adult subjects received vaccinations alone (N = 42, control) or in combination with 160 mg IXE subcutaneously 2 weeks prior to vaccination and 80 mg IXE on the day of vaccination (N = 41, IXE)...
November 7, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/29110556/the-impact-of-biologic-agents-on-health-related-quality-of-life-outcomes-in-patients-with-psoriasis
#13
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/29109267/protein-engineering-of-the-chemokine-ccl20-prevents-psoriasiform-dermatitis-in-an-il-23-dependent-murine-model
#14
A E Getschman, Y Imai, O Larsen, F C Peterson, X Wu, M M Rosenkilde, S T Hwang, B F Volkman
Psoriasis is a chronic inflammatory skin disease characterized by the infiltration of T cell and other immune cells to the skin in response to injury or autoantigens. Conventional, as well as unconventional, γδ T cells are recruited to the dermis and epidermis by CCL20 and other chemokines. Together with its receptor CCR6, CCL20 plays a critical role in the development of psoriasiform dermatitis in mouse models. We screened a panel of CCL20 variants designed to form dimers stabilized by intermolecular disulfide bonds...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29103334/a-systematic-review-of-active-comparator-controlled-clinical-trials-in-patients-with-moderate-to-severe-psoriasis
#15
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
#16
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/29074858/high-fat-diet-exacerbates-murine-psoriatic-dermatitis-by-increasing-the-number-of-il-17-producing-%C3%AE-%C3%AE-t-cells
#17
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
#18
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/29051036/characterization-of-disease-burden-comorbidities-and-treatment-use-in-a-large-us-based-cohort-results-from-the-corrona-psoriasis-registry
#19
Bruce Strober, Chitra Karki, Marc Mason, Ning Guo, Stacey H Holmgren, Jeffrey D Greenberg, Mark Lebwohl
BACKGROUND: Psoriasis is an immunodysregulatory inflammatory disease associated with comorbidities impacting quality of life. With the advent of new treatments, there is growing need to assess the long term safety and efficacy of treatments in a real-world setting. OBJECTIVES: The objective of the Corrona Psoriasis Registry is to study the comparative safety and efficacy of FDA approved biologic treatments. METHODS: A cross-sectional study of patients enrolled in the registry, who initiated/switched to a systemic therapy at enrollment/previous 12 months...
October 16, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29043884/guselkumab-for-psoriasis-a-critical-appraisal-of-phase-iii-studies
#20
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
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