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Il-23 and psoriasis

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https://www.readbyqxmd.com/read/28026823/anti%C3%A2-cytokine-therapy-for-psoriasis-not-only-tnf%C3%A2-%C3%AE-blockers-overview-of-reports-on-the-effectiveness-of-therapy-with-il%C3%A2-12-il%C3%A2-23-and-t-and-b-lymphocyte-inhibitors
#1
Dominika Wcisło-Dziadecka, Martyna Zbiciak, Ligia Brzezińska-Wcisło, Urszula Mazurek
TNF‑α inhibitors - infliximab, etanercept and adalimumab - can be used in the treatment of psoriasis vulgaris and psoriatic arthritis, along with other inhibitors of proinflammatory cytokines, such as interleukin‑12 (IL‑12) and IL‑23. This paper presents the results of research on the use of biological drugs other than the tumor necrosis factor blockers (TNF‑α), namely inhibitors of IL‑12 and IL‑23 (ustekinumab), T‑cell inhibitors (alefacept and efalizumab), B‑cell inhibitors (rituximab), anti‑IL‑17 agents (secukinumab, ixekizumab, and brodalumab) and IL23p19 inhibitors (guselkumab and tildrakizumab)...
December 8, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28011143/dynamic-changes-in-resident-and-infiltrating-epidermal-dendritic-cells-in-active-and-resolved-psoriasis
#2
Elisa Martini, Maria Wiken, Stanley Cheuk, Irène Gallais Sérézal, Faezzah Baharom, Mona Ståhle, Anna Smed-Sörensen, Liv Eidsmo
Epidermal Langerhans cells (LCs) are spatially separated from dermal dendritic cells (DCs) in healthy human skin. In active psoriasis, maintained by local production of IL-23 and IL-17, DCs infiltrate both skin compartments. Here we show that CCR2(+) epidermal DCs (eDCs), phenotypically distinct from dermal DCs, were strictly confined to lesional psoriasis. The eDCs exceeded the number of LCs and displayed high expression of genes involved in neutrophil recruitment and the activation of keratinocytes and T cells...
December 20, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27999243/serum-levels-of-il-10-and-il-22-cytokines-in-patients-with-psoriasis
#3
Mohammad Reza Sobhan, Mahmood Farshchian, Ali Hoseinzadeh, Hamid Reza Ghasemibasir, Ghasem Solgi
BACKGROUND: As a chronic inflammatory condition, psoriasis results from an interaction between genetic and immunologic factors in a predisposing environment. In spite of compelling evidence for the role of T cells and cytokines in psoriasis, interleukin (IL)-10 and IL-22 have not been sufficiently investigated. OBJECTIVE: To assess the serum levels of IL-10 and IL-22 in patients with psoriasis compared to healthy controls. METHODS: A total of 28 patients with psoriasis were compared with 28 age and sex-matched healthy subjects...
December 2016: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/27984001/psoriatic-inflammation-enhances-allergic-airway-inflammation-through-il-23-stat3-signaling-in-a-murine-model
#4
Ahmed Nadeem, Naif O Al-Harbi, Mushtaq A Ansari, Mohammed M Al-Harbi, Ahmed M El-Sherbeeny, Khairy M A Zoheir, Sabry M Attia, Mohamed M Hafez, Othman A Al-Shabanah, Sheikh F Ahmad
Psoriasis is an autoimmune inflammatory skin disease characterized by activated IL-23/STAT3/Th17 axis. Recently psoriatic inflammation has been shown to be associated with asthma. However, no study has previously explored how psoriatic inflammation affects airway inflammation. Therefore, this study investigated the effect of imiquimod (IMQ)-induced psoriatic inflammation on cockroach extract (CE)-induced airway inflammation in murine models. Mice were subjected to topical and intranasal administration of IMQ and CE to develop psoriatic and airway inflammation respectively...
January 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27982014/monocyte-derived-inflammatory-langerhans-cells-and-dermal-dendritic-cells-mediate-psoriasis-like-inflammation
#5
Tej Pratap Singh, Howard H Zhang, Izabela Borek, Peter Wolf, Michael N Hedrick, Satya P Singh, Brian L Kelsall, Bjorn E Clausen, Joshua M Farber
Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined. Here we show that DCs are required for psoriasis-like changes in mouse skin induced by the local injection of IL-23. However, Flt3L-dependent DCs and resident Langerhans cells are dispensable for the inflammation. In epidermis and dermis, the critical DCs are TNF-producing and IL-1β-producing monocyte-derived DCs, including a population of inflammatory Langerhans cells. Depleting Ly6C(hi) blood monocytes reduces DC accumulation and the skin changes induced either by injecting IL-23 or by application of the TLR7 agonist imiquimod...
December 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27964879/activation-of-langerhans-cells-promotes-the-inflammation-in-imiquimod-induced-psoriasis-like-dermatitis
#6
Chunying Xiao, Zhenlai Zhu, Shuhong Sun, Jixin Gao, Meng Fu, Yufeng Liu, Gang Wang, Xu Yao, Wei Li
BACKGROUND: Langerhans cells (LCs) are epidermis-resident dendritic cells that sense and mediate stimuli from skin and outside world, and participate in various skin diseases, playing either pro-inflammatory or regulatory roles. However, the exact function of LCs in the pathogenesis of psoriasis remains unclear, and the conclusions of previous studies are controversial. OBJECTIVES: To explore the role of LCs in mouse model of imiquimod (IMQ)-induced psoriasis-like dermatitis using langerin-diphtheria toxin A (DTA) mice that are constitutively deficient in LCs...
December 5, 2016: Journal of Dermatological Science
https://www.readbyqxmd.com/read/27964744/differential-gene-and-protein-expression-of-chemokines-and-cytokines-in-synovial-fluid-of-patients-with-arthritis
#7
Anastasiya Muntyanu, Fatima Abji, Kun Liang, Remy A Pollock, Vinod Chandran, Dafna D Gladman
BACKGROUND: Psoriatic arthritis (PsA), an inflammatory musculoskeletal disease, develops in approximately 30% of patients with psoriasis. Previously, chemokine (C-X-C motif) ligand 10 (CXCL10) was identified as a predictive biomarker of PsA in patients with psoriasis and was reduced after development of PsA. The purpose of the present study was to explore messenger RNA (mRNA) and protein expression of CXCL10 and its receptor, chemokine (C-X-C motif) receptor 3 (CXCR3), in the joints of patients with PsA to gain insight into their role in the pathogenesis of the disease...
December 13, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27956825/ustekinumab-in-treatment-of-crohn-s-disease-design-development-and-potential-place-in-therapy
#8
REVIEW
Parakkal Deepak, Edward V Loftus
Crohn's disease is characterized by a dysregulation of both innate and adaptive immunity responses. Interleukin-12/23 (IL-12/23) pathway has been found to be a major driver of inflammation in adaptive immune responses. Ustekinumab is a fully human immunoglobulin G1 kappa monoclonal antibody that blocks the p40 subunit of IL-12 and IL-23 and prevents their interaction with their cell surface receptor and further cytokine activation. It is currently approved in the management of plaque psoriasis and psoriatic arthritis...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27942589/interleukin-6-regulates-psoriasiform-inflammation-associated-thrombosis
#9
Yunmei Wang, Jackelyn B Golden, Yi Fritz, Xiufen Zhang, Doina Diaconu, Maya I Camhi, Huiyun Gao, Sean M Dawes, Xianying Xing, Santhi K Ganesh, Johann E Gudjonsson, Daniel I Simon, Thomas S McCormick, Nicole L Ward
Psoriasis patients are at increased risk of heart attack and stroke and have elevated MRP8/14 levels that predict heart attack. The KC-Tie2 psoriasiform mouse model exhibits elevated MRP8/14 and is prothrombotic. Mrp14(-/-) mice, in contrast, are protected from thrombosis, but, surprisingly, KC-Tie2xMrp14(-/-) mice remain prothrombotic. Treating KC-Tie2xMrp14(-/-) mice with anti-IL-23p19 antibodies reversed the skin inflammation, improved thrombosis, and decreased IL-6. In comparison, IL-6 deletion from KC-Tie2 animals improved thrombosis despite sustained skin inflammation, suggesting that thrombosis improvements following IL-23 inhibition occur secondary to IL-6 decreases...
December 8, 2016: JCI Insight
https://www.readbyqxmd.com/read/27934944/overexpression-of-glucocorticoid-induced-leucine-zipper-gilz-increases-susceptibility-to-imiquimod-induced-psoriasis-and-involves-cutaneous-activation-of-tgf-%C3%AE-1
#10
Elena Carceller, Marlies Ballegeer, Julie Deckers, Carlo Riccardi, Stefano Bruscoli, Tino Hochepied, Claude Libert, Paloma Pérez
Psoriasis vulgaris is a chronic inflammatory skin disease affecting millions of people. Its pathophysiology is complex and involves a skin compartment with epidermal and immune cells which produce cytokines, e.g. belonging to the IL-23-Th17-cell axis. Glucocorticoids (GCs) are the most common therapeutics used in cutaneous inflammatory disorders and GC-induced leucine zipper (GILZ) has emerged as a mediator of GCs due to its anti-inflammatory actions, theoretically lacking GC side-effects. We evaluated whether GILZ may provide a better therapeutic index in comparison to GCs during the onset and progression of psoriasis by generating and characterizing a mouse model with generalized overexpression of this protein (GILZ-Tg mice) and the imiquimod (IMQ) psoriasis model...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27926724/new-anti-il-23-drugs-raise-hopes-for-psoriasis-plaque-clearance
#11
Elie Dolgin
No abstract text is available yet for this article.
December 7, 2016: Nature Biotechnology
https://www.readbyqxmd.com/read/27905482/pharmacologic-modulation-of-ror%C3%AE-t-translates-to-efficacy-in-preclinical-and-translational-models-of-psoriasis-and-inflammatory-arthritis
#12
Xiaohua Xue, Pejman Soroosh, Aimee De Leon-Tabaldo, Rosa Luna-Roman, Marciano Sablad, Natasha Rozenkrants, Jingxue Yu, Glenda Castro, Homayon Banie, Wai-Ping Fung-Leung, Luis Santamaria-Babi, Thomas Schlueter, Michael Albers, Kristi Leonard, Alison L Budelsky, Anne M Fourie
The IL-23/IL-17 pathway is implicated in autoimmune diseases, particularly psoriasis, where biologics targeting IL-23 and IL-17 have shown significant clinical efficacy. Retinoid-related orphan nuclear receptor gamma t (RORγt) is required for Th17 differentiation and IL-17 production in adaptive and innate immune cells. We identified JNJ-54271074, a potent and highly-selective RORγt inverse agonist, which dose-dependently inhibited RORγt-driven transcription, decreased co-activator binding and promoted interaction with co-repressor protein...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27892456/il-12-protects-from-psoriasiform-skin-inflammation
#13
Paulina Kulig, Stephanie Musiol, Sandra Nicole Freiberger, Bettina Schreiner, Gabor Gyülveszi, Giancarlo Russo, Stanislav Pantelyushin, Kenji Kishihara, Francesca Alessandrini, Thomas Kündig, Federica Sallusto, Günther F L Hofbauer, Stefan Haak, Burkhard Becher
Neutralization of the common p40-subunit of IL-12/23 in psoriasis patients has led to a breakthrough in the management of moderate to severe disease. Aside from neutralizing IL-23, which is thought to be responsible for the curative effect, anti-p40 therapy also interferes with IL-12 signalling and type 1 immunity. Here we dissect the individual contribution of these two cytokines to the formation of psoriatic lesions and understand the effect of therapeutic co-targeting of IL-12 and IL-23 in psoriasis. Using a preclinical model for psoriatic plaque formation we show that IL-12, in contrast to IL-23, has a regulatory function by restraining the invasion of an IL-17-committed γδT (γδT17) cell subset...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27883001/psoriasis
#14
Jacqueline E Greb, Ari M Goldminz, James T Elder, Mark G Lebwohl, Dafna D Gladman, Jashin J Wu, Nehal N Mehta, Andrew Y Finlay, Alice B Gottlieb
Psoriasis is a chronic, immune-mediated disorder with cutaneous and systemic manifestations and substantial negative effects on patient quality of life. Psoriasis has a strong, albeit polygenic, genetic basis. Whereas approximately half of the accountable genetic effect of psoriasis maps to the major histocompatibility complex, >70 other loci have been identified, many of which implicate nuclear factor-κB, interferon signalling and the IL-23-IL-23 receptor axis. Psoriasis pathophysiology is characterized by abnormal keratinocyte proliferation and immune cell infiltration in the dermis and epidermis involving the innate and adaptive immune systems, with important roles for dendritic cells and T cells, among other cells...
November 24, 2016: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/27868150/clinical-efficiency-of-topical-calcipotriol-betamethasone-treatment-in-psoriasis-relies-on-suppression-of-the-inflammatory-tnf%C3%AE-il-23-il-17-axis
#15
Minna E Kubin, Nina Kokkonen, Riitta Palatsi, Päivi M Hägg, Juha P Väyrynen, Virpi Glumoff, Kirsi-Maria Haapasaari, Tiina Hurskainen, Kaisa Tasanen
The effects of topical calcipotriol/betamethasone combination therapy and betamethasone monotherapy on inflammatory T cell numbers and molecular markers were compared in patients with psoriasis. Combination therapy down-regulated the expression of tumour necrosis factor (TNF)-α, interleukin (IL)-23A, IL-17A, S100A7, CCL-20 and interferon (IFN)-γ in skin and TNF-α, IL-6, IL-23A, T-bet and IFN-γ in peripheral blood mononuclear cells (PBMCs). Betamethasone monotherapy had less effect. Expression of FoxP3 in both skin and PBMCs was down-regulated by calcipotriol/betamethasone, but not by betamethasone...
November 21, 2016: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/27836567/management-of-psoriatic-arthritis-early-diagnosis-monitoring-of-disease-severity-and-cutting-edge-therapies
#16
REVIEW
Siba P Raychaudhuri, Reason Wilken, Andrea C Sukhov, Smriti K Raychaudhuri, Emanual Maverakis
Psoriatic arthritis (PsA) is a heterogeneous disease that can involve a variety of distinct anatomical sites including a patient's peripheral and axial joints, entheses, skin and nails. Appropriate management of PsA requires early diagnosis, monitoring of disease activity, and utilization of cutting edge therapies. To accomplish the former there are a variety of PsA-specific tools available to screen, diagnose, and assess patients. This review will outline the recently developed PsA screening tools, including the Toronto Psoriatic Arthritis Screening Questionnaire (TOPAS), the Psoriasis Epidemiology Screening Tool (PEST), the Psoriatic Arthritis Screening and Evaluation (PASE), and the Psoriasis and Arthritis Screening Questionnaire (PASQ)...
January 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27824222/association-between-endocrinological-immunological-and-psychosocial-variables-in-psoriasis-patients
#17
Özlem Bilgiç, Ayhan Bilgiç, Abdullah Sivrikaya, Yavuz Selvi, Ali Ünlü, Hilmi C Altinyazar
BACKGROUND: There is limited data concerning the relationship between psychosocial problems of psoriasis patients and the function of their hypothalamic-pituitary-adrenal (HPA) axis and immunologic markers. This study aimed to determine serum levels of basal cortisol and adrenocorticotropic hormone (ACTH) and circulating levels of various cytokines and chemokines and their association with psychological measures in psoriasis patients. METHODS: Serum concentrations of endocrinological and immunological variables were quantified, and psychiatric questionnaires were completed...
December 2016: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/27810232/potential-role-of-il-17-producing-cd4-cd8-double-negative-%C3%AE-%C3%AE-t-cells-in-psoriatic-skin-inflammation-in-a-tpa-induced-stat3c-transgenic-mouse-model
#18
Azumi Ueyama, Chihiro Imura, Yasuyuki Fusamae, Kenichiro Tsujii, Yoko Furue, Miwa Aoki, Minoru Suzuki, Tomohiko Okuda, Itsuki Oshima, Kiyoshi Yasui, Michitaka Shichijo, Mina Yamamoto
BACKGROUND: Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders and is accompanied by erythematous scaly plaques. There is growing evidence that the IL-23/Th17 axis plays a critical role in development of the disease. It was recently shown that in addition to CD4(+) Th17 cells, various IL-17-producing cell subsets such as CD8(+) Tc17 cells, dermal γδ T cells, and innate lymphoid cells are also involved in the development of psoriatic inflammation in humans...
January 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/27765025/staphylococcus-aureus-bacteremia-with-iliac-artery-endarteritis-in-a-patient-receiving-ustekinumab
#19
Insa Joost, Johannes Steinfurt, Philipp T Meyer, Winfried V Kern, Siegbert Rieg
BACKGROUND: Ustekinumab (Stelara®), a human monoclonal antibody targeting the p40-subunit of interleukin (IL)-12 and IL-23, is indicated for moderate to severe plaque psoriasis and psoriatic arthritis. In large multicenter, prospective trials assessing efficacy and safety of ustekinumab increased rates of severe infections have not been observed so far. CASE PRESENTATION: Here, we report the case of a 64-year old woman presenting with chills, pain and swelling of her right foot with dark maculae at the sole, and elevated inflammatory markers...
October 20, 2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27743912/palmoplantar-pustular-psoriasis-pppp-is-characterized-by-activation-of-the-il-17a-pathway
#20
Robert Bissonnette, Judilyn Fuentes-Duculan, Shunya Mashiko, Xuan Li, Kathleen M Bonifacio, Inna Cueto, Mayte Suárez-Fariñas, Catherine Maari, Chantal Bolduc, Simon Nigen, Marika Sarfati, James G Krueger
BACKGROUND: Palmoplantar pustular psoriasis (PPPP) is a variant of psoriasis, which has significant negative impact on quality of life. The cellular and molecular inflammatory pathways involved in PPPP have not been well studied. OBJECTIVE: Study the expression of cytokines and chemokines involved in the IL-17/IL-23 axis in palmoplantar pustular psoriasis and other difficult to treat psoriasis areas (palms, scalp, elbows and lower legs). METHODS: Skin biopsies were performed on a total of 80 patients with PPPP, non-pustular palmoplantar psoriasis (NPPPP), or psoriasis located on elbows, knees and scalp as well as 10 healthy subjects...
January 2017: Journal of Dermatological Science
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