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https://www.readbyqxmd.com/read/28653490/the-role-of-il-23-and-the-il-23-th-17-immune-axis-in-the-pathogenesis-and-treatment-of-psoriasis
#1
REVIEW
G Girolomoni, R Strohal, L Puig, H Bachelez, J Barker, W H Boehncke, J C Prinz
Psoriasis is a chronic, immune-mediated disease affecting more than 100 million people worldwide and up to 2.2% of the UK population. The etiology of psoriasis is thought to originate from an interplay of genetic, environmental, infectious, and lifestyle factors. The manner in which genetic and environmental factors interact to contribute to the molecular disease mechanisms has remained elusive. However, the interleukin 23 (IL-23)/T-helper 17 (TH 17) immune axis has been identified as a major immune pathway in psoriasis disease pathogenesis...
June 27, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28650001/brodalumab-the-first-anti-il-17-receptor-agent-for-psoriasis
#2
L Puig
Psoriasis is a chronic immune-mediated inflammatory skin disease in which the alteration of the interleukin-23 (IL-23)/IL-17 cytokine axis appears to be crucial from a pathogenetic perspective. This has been confirmed by the efficacy of monoclonal antibodies blocking IL-17A, such as secukinumab and ixekizumab. Brodalumab is a human anti-IL-17 receptor A (IL-17RA) monoclonal antibody that inhibits the biological activity of IL-17A, IL-17F and other IL-17 isoforms, and has been approved (210 mg s.c. at weeks 0, 1, 2 and every 2 weeks thereafter) for the treatment of psoriasis vulgaris, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma in Japan (Lumicef)...
May 2017: Drugs of Today
https://www.readbyqxmd.com/read/28646856/the-imbalance-of-th17-treg-cells-is-involved-in-the-progression-of-nonalcoholic-fatty-liver-disease-in-mice
#3
Beihui He, Liyan Wu, Wei Xie, Yitong Shao, Jianping Jiang, Zhenzhong Zhao, Maoxiang Yan, Zhiyun Chen, Dawei Cui
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common, chronic liver disease worldwide. Recent studies have shown that T helper (Th) 17 and regulatory T (Treg) cells play critical roles in various disorders of liver inflammation. Here, we explored the value of polyene phosphatidylcholine capsules (PPC) for regulating the imbalance of Th17/Treg cells in the pathogenesis of mice with NAFLD. METHODS: C57BL/6 mice were randomly divided into three groups as follows:normal diet (ND), high-fat diet (HF),and HF plus PPC(HF + PPC)...
June 24, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28646393/the-changing-landscape-of-alopecia-areata-the-therapeutic-paradigm
#4
REVIEW
Yael Renert-Yuval, Emma Guttman-Yassky
Alopecia areata (AA), a prevalent inflammatory cause of hair loss, lacks FDA-approved therapeutics for extensive cases, which are associated with very poor rates of spontaneous hair regrowth and major psychological distress. Current treatments for severe cases include broad immune-suppressants, which are associated with significant adverse effects, precluding long-term use, with rapid hair loss following treatment termination. As a result of the extent of the disease in severe cases, topical contact sensitizers and intralesional treatments are of limited use...
June 23, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28646040/il-23-limits-the-production-of-il-2-and-promotes-autoimmunity-in-lupus
#5
Hong Dai, Fan He, George C Tsokos, Vasileios C Kyttaris
The IL-23/IL-17 pathway is important in multiple autoimmune diseases, but its effect on lupus pathology remains unclear, with opposing trials in murine models of the disease. In this study, we show a disease activity-related upregulation of serum IL-23 and IL-23 receptor in patients with systemic lupus erythematosus (SLE) as compared with healthy controls. When added in SLE T cell in vitro cultures, IL-23 induced IL-17 and limited IL-2 production, whereas T follicular helper and double negative (DN) T cells significantly expanded...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28642279/role-of-myd88-signaling-in-the-imiquimod-induced-mouse-model-of-psoriasis-focus-on-innate-myeloid-cells
#6
Sara Costa, Olivia Marini, Dalila Bevilacqua, Anthony L DeFranco, Baidong Hou, Silvia Lonardi, William Vermi, Pamela Rodegher, Anna Panato, Franco Tagliaro, Clifford A Lowell, Marco A Cassatella, Giampiero Girolomoni, Patrizia Scapini
Psoriasis is a chronic skin disease associated with deregulated activation of immune cells and keratinocytes. In this study, we used the imiquimod (IMQ)-induced mouse model of psoriasis to dissect better the contribution of hematopoietic and skin-resident stromal cells to psoriasis development. The comparison of disease development in mice carrying the hematopoietic cell-specific deletion of MyD88 (Myd88(fl/fl)Vav-cre(+) mice) with mice carrying the total MyD88 deficiency (Myd88(-/-) mice), we show that the progression of skin and systemic inflammation, as well as of epidermal thickening, was completely dependent on MyD88 expression in hematopoietic cells...
June 22, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28642092/chemokine-ccl17-is-expressed-by-dendritic-cells-in-the-cns-during-experimental-autoimmune-encephalomyelitis-and-promotes-pathogenesis-of-disease
#7
Christina Ruland, Hannes Renken, Ivan Kuzmanov, Arezoo Fattahi Mehr, Kathrin Schwarte, Manuela Cerina, Alexander Herrmann, David-Marian Otte, Andreas Zimmer, Nicholas Schwab, Sven G Meuth, Volker Arolt, Luisa Klotz, Irmgard Förster, Stefanie Scheu, Judith Alferink
The CC chemokine ligand 17 (CCL17) and its cognate CC chemokine receptor 4 (CCR4) are known to control leukocyte migration, maintenance of TH17 cells, and regulatory T cell (Treg) expansion in vivo. In this study we characterized the expression and functional role of CCL17 in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Using a CCL17/EGFP reporter mouse model, we could show that CCL17 expression in the CNS can be found in a subset of classical dendritic cells (DCs) that immigrate into the CNS during the effector phase of MOG-induced EAE...
June 19, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28639011/guselkumab-for-the-treatment-of-psoriasis-a-review-of-phase-iii-trials
#8
REVIEW
Mio Nakamura, Katherine Lee, Caleb Jeon, Sahil Sekhon, Ladan Afifi, Di Yan, Kristina Lee, Tina Bhutani
INTRODUCTION: Interleukin (IL)-23 inhibitors are a new class of biologics currently undergoing clinical trials for the treatment of moderate-to-severe psoriasis. Phase III studies of guselkumab, an IL-23 receptor monoclonal antibody, are currently underway. METHODS: We summarize the available phase III results to date, establishing the efficacy and safety of guselkumab in patients with moderate-to-severe plaque psoriasis. RESULTS: Currently, there are available data of up to 48 weeks from two Phase III, multicenter, randomized, double-blind, placebo- and comparator-controlled clinical trials, VOYAGE 1 and VOYAGE 2...
June 21, 2017: Dermatology and Therapy
https://www.readbyqxmd.com/read/28637904/ifn-%C3%AE-expressing-th17-cells-are-required-for-development-of-severe-ocular-surface-autoimmunity
#9
Yihe Chen, Sunil K Chauhan, Chunyi Shao, Masahiro Omoto, Takenori Inomata, Reza Dana
Th17 cells are critical effectors mediating the ocular surface autoimmunity in dry eye disease (DED). Increased IFN-γ has also been implicated in DED; however, it remains unclear to what extent Th1 cells contribute to DED pathogenesis. In this study, we investigated the cellular source of IFN-γ and assessed its contribution to corneal epitheliopathy in DED mice. We discovered a significant IL-17A(+)IFN-γ(+) (Th17/1) population and determined that these cells are derived from Th17 precursors. Adoptive transfer of Th17/1, but not Th1, cells confers the disease to naive recipients as effectively as do Th17 cells alone...
June 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28635548/th-17-regulatory-cytokines-il-21-il-23-and-il-6-enhance-neutrophil-production-of-il-17-cytokines-during-asthma
#10
Rabih Halwani, Asma Sultana, Alejandro Vazquez-Tello, Amer Jamhawi, Abeer A Al-Masri, Saleh Al-Muhsen
BACKGROUND: In a subset of severe asthma patients, chronic airway inflammation is associated with infiltration of neutrophils, Th-17 cells and elevated expression of Th-17-derived cytokines (e.g., interleukin [IL]-17, IL-21, IL-22). Peripheral neutrophils from allergic asthmatics are known to express higher IL-17 cytokine levels than those from healthy subjects, but the regulatory mechanisms involved are not well understood. We hypothesize that Th-17 regulatory cytokines could modulate IL-17 expression in neutrophils...
March 2, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28634882/gingipain-of-porphyromonas-gingivalis-manipulates-m1-macrophage-polarization-through-c5a-pathway
#11
Yubo Hou, Haiyan Yu, Xinchan Liu, Gege Li, Jiahui Pan, Changyu Zheng, Weixian Yu
Gingipains secreted by Porphyromonas gingivalis (P. gingivalis, Pg) play an important role in maintaining macrophage infiltrating. And, this study is to evaluate effects of gingipain on M1 macrophage polarization after exposure to Porphyromonas gingivalis (P. gingivalis, Pg) and if these effects are through complement component 5a (C5a) pathway. Mouse RAW264.7 macrophages were exposed to gingipain extracts, Escherichia coli lipopolysaccharides (Ec-LPS), Pg-LPS with or without the C5aR antagonist: PMX-53 for 24 h...
June 20, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28634654/improvement-in-latent-variable-indirect-response-modeling-of-multiple-categorical-clinical-endpoints-application-to-modeling-of-guselkumab-treatment-effects-in-psoriatic-patients
#12
Chuanpu Hu, Bruce Randazzo, Amarnath Sharma, Honghui Zhou
Exposure-response modeling plays an important role in optimizing dose and dosing regimens during clinical drug development. The modeling of multiple endpoints is made possible in part by recent progress in latent variable indirect response (IDR) modeling for ordered categorical endpoints. This manuscript aims to investigate the level of improvement achievable by jointly modeling two such endpoints in the latent variable IDR modeling framework through the sharing of model parameters. This is illustrated with an application to the exposure-response of guselkumab, a human IgG1 monoclonal antibody in clinical development that blocks IL-23...
June 20, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28634408/a-tightly-regulated-il-22-response-maintains-immune-functions-and-homeostasis-in-systemic-viral-infection
#13
Panpan Yi, Yuejin Liang, Denley Ming Kee Yuan, Zuliang Jie, Zakari Kwota, Yan Chen, Yingzi Cong, Xuegong Fan, Jiaren Sun
Interleukin-22 (IL-22) plays an important role in host immunity and tissue homeostasis in infectious and inflammatory diseases. However, the function and regulation of IL-22 in viral infection remain largely unknown. Here, we report that viral infection triggered early IL-22 production from the liver and lymphoid organs. γδ T cells are the main immune cells to produce IL-22 in the liver, a process mediated by the IL-23/phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634033/nickel-sulfate-promotes-il-17a-producing-cd4-t-cells-by-an-il-23-dependent-mechanism-regulated-by-tlr4-and-jak-stat-pathways
#14
Rami Bechara, Diane Antonios, Hayat Azouri, Marc Pallardy
Allergic contact dermatitis, caused by nickel, is a delayed-type hypersensitivity reaction and 14.5% of the general population may be affected in Europe. Among a wide range of cytokines, the IL-12 family has unique structural and immunological characteristics. While IL-12p70 promotes T helper (Th) 1 cells polarization, IL-23 promotes Th17 cells development and both have been isolated from nickel-allergic patients. In this work, we were interested in understanding the mechanism behind nickel-induced Th17 cells development...
June 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28630387/assessment-of-t-helper-17-associated-cytokines-in-third-trimester-of-pregnancy
#15
Tahereh Poordast, Fateme Sadat Najib, Rasoul Baharlou, Atena Bijani, Shaghayegh Moradi Alamdarloo, Alieh Poordast
BACKGROUND: Preeclampsia is a common pregnancy-specific disorder associated with significant maternal and fetal morbidity and mortality worldwide. It has been proposed that the imbalance between two CD4+ T cell subtypes, regulatory T cells (Treg) and T-helper 17 cells (Th17), is involved in the pathophysiology of preeclampsia. OBJECTIVES: To determine the serum levels of IL-17, IL-21, IL-23 and TGF-β in patients with preeclampsia. METHODS: Blood samples were collected from 30 preeclampsia patients, 30 normotensive pregnant women and 30 healthy individuals with no history of malignancies or autoimmune disorders based on simple sampling...
June 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28630278/synthetic-deletion-of-the-interleukin-23-receptor-il-23r-stalk-region-led-to-autonomous-il-23r-homodimerization-and-activation
#16
Thorben M Hummel, Theresa Ackfeld, Marco Schönberg, Gregor Ciupka, Falk Schulz, Anne Oberdoerster, Joachim Grötzinger, Jürgen Scheller, Doreen M Floss
Interleukin 23 (IL-23) regulates the development of TH17 cells, which are important for antimicrobial and antifungal responses, autoimmune and chronic inflammatory diseases. IL-23-induced Jak/STAT signaling is mediated via the heterodimeric IL-23 receptor (IL-23R):IL-12 receptor β1 (IL-12Rβ1) complex. The typical signal-transducing receptor of the IL-6/IL-12 family contains three extracellular membrane proximal FNIII-type domains, which are not involved in cytokine binding but mandatory for signal transduction...
June 19, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28619037/ifn-%C3%AE-1-with-th17-axis-cytokines-and-ifn-%C3%AE-define-different-subsets-in-systemic-lupus-erythematosus-sle
#17
Vilija Oke, Susanna Brauner, Anders Larsson, Johanna Gustafsson, Agneta Zickert, Iva Gunnarsson, Elisabet Svenungsson
BACKGROUND: Interferon (IFN)-α is thought to have a pivotal role in systemic lupus erythematosus (SLE), and type III IFNs (IFN-λ) were recently also associated with SLE. In this study, we measured levels of IFN-α, IFN-λ1, and related cytokines, such as IL-17A, IL-23, and interferon-γ-induced protein 10 (IP-10), in a Karolinska University Hospital cohort of patients with SLE and control subjects. The objective of the study was to investigate if cytokine measurements could identify different subsets of patients with active SLE and higher disease damage...
June 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28612601/classification-of-bladder-cancer-patients-via-penalized-linear-discriminant-analysis
#18
Hadi Raeisi Shahraki, Peyman Bemani, Maryam Jalali
Objectives: In order to identify genes with the greatest contribution to bladder cancer, we proposed a sparse model making the best discrimination from other patients. Methods: In a cross-sectional study, 22 genes with a key role in most cancers were considered in 21 bladder cancer patients and 14 participants of the same age (± 3 years) without bladder cancer in Shiraz city, Southern Iran. Real time-PCR was carried out using SYBR Green and for each of the 22 target genes 2-Δct as a quantitative index of gene expression was reported...
May 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28609751/aneurysmal-subarachnoid-hemorrhage-lead-to-systemic-upregulation-of-il-23-il-17-inflammatory-axis
#19
Shafqat Rasul Chaudhry, Erdem Güresir, Hartmut Vatter, Thomas M Kinfe, Dirk Dietrich, Alf Lamprecht, Sajjad Muhammad
IL-23 and IL-17 are pro-inflammatory cytokines. IL-23 is secreted by activated macrophages and dendritic cells, while IL-17 by Th17 cells. Serum IL-23 and IL-17 are known to be elevated in numerous inflammatory diseases including neurodegenerative diseases. The role of serum IL-23 and IL-17 in aneurysmal subarachnoid hemorrhage (aSAH) has still not been investigated. The present work investigates the serum IL-23 and IL-17 levels and their association with post hemorrhagic complications and clinical outcome in patients with aSAH...
June 10, 2017: Cytokine
https://www.readbyqxmd.com/read/28609384/cytokine-profiles-in-osteoporosis-suggest-a-proresorptive-bias
#20
Fawaz Azizieh, Raj Raghupathy, Diaa Shehab, Khaled Al-Jarallah, Renu Gupta
OBJECTIVE: As the immune system is suggested to contribute to the pathophysiology of osteoporosis in menopause, we compared the levels of proresorptive and antiresorptive cytokines produced by peripheral blood mononuclear cells (PBMCs) from postmenopausal women with normal and low bone mineral density (BMD). METHODS: Seventy-one postmenopausal women were studied; 25 had normal BMD and 46 had low BMD. Participants were categorized as normal (n = 25), osteopenic (n = 31), and osteoporotic (n = 15) based on T-scores...
June 19, 2017: Menopause: the Journal of the North American Menopause Society
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