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IL-17 and psoriasis

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https://www.readbyqxmd.com/read/29774240/mannan-induced-nos2-in-macrophages-enhances-il-17-driven-psoriatic-arthritis-by-innate-lymphocytes
#1
Jianghong Zhong, Tatjana Scholz, Anthony C Y Yau, Simon Guerard, Ulrike Hüffmeier, Harald Burkhardt, Rikard Holmdahl
Previous identification of the inducible nitric oxide synthase (NOS2) gene as a risk allele for psoriasis (Ps) and psoriatic arthritis (PsA) suggests a possible pathogenic role of nitric oxide (NO). Using a mouse model of mannan-induced Ps and PsA (MIP), where macrophages play a regulatory role by releasing reactive oxygen species (ROS), we found that NO was detectable before disease onset in mice, independent of a functional nicotinamide adenine dinucleotide phosphate oxidase 2 complex. MIP was suppressed by either deletion of Nos2 or inhibition of NO synthases with NG-nitro-l-arginine methyl ester, demonstrating that Nos2-derived NO is pathogenic...
May 2018: Science Advances
https://www.readbyqxmd.com/read/29759005/ido-expressing-fibroblasts-suppress-the-development-of-imiquimod-induced-psoriasis-like-dermatitis
#2
Sanam Salimi Elizei, Mohammadreza Pakyari, Mehraneh Ghoreishi, Ruhangiz Kilani, Sanaz Mahmoudi, Aziz Ghahary
Psoriasis is a chronic skin condition whose pathogenesis is reported to be due to the activation of the interleukin-23/interleukin-17 (IL-23/IL-17) pathway. Here, we report that indoleamine 2,3-dioxygenase (IDO)-expressing fibroblasts reduce the activity of this pathway in activated immune cells. The findings showed that intralesional injection of IDO-expressing fibroblasts in imiquimod-induced psoriasis-like dermatitis on the back and ear (Pso. ear group) in mice significantly improves the clinical lesional appearance by reducing the number of skin-infiltrated IL-17+ CD4+ T cells (1...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29757188/microrna-210-overexpression-promotes-psoriasis-like-inflammation-by-inducing-th1-and-th17-cell-differentiation
#3
Ruifang Wu, Jinrong Zeng, Jin Yuan, Xinjie Deng, Yi Huang, Lina Chen, Peng Zhang, Huan Feng, Zixin Liu, Zijun Wang, Xiaofei Gao, Haijing Wu, Honglin Wang, Yuwen Su, Ming Zhao, Qianjin Lu
Immune imbalance of T lymphocyte subsets is a hallmark of psoriasis, but the molecular mechanisms underlying this aspect of psoriasis pathology are poorly understood. Here, we report that microRNA-210 (miR-210), a miR that is highly expressed in both psoriasis patients and mouse models, induces helper T (Th) 17 and Th1 cell differentiation but inhibits Th2 differentiation through repressing STAT6 and LYN expression, contributing to several aspects of the immune imbalance in psoriasis. Both miR-210 ablation in mice and inhibition of miR-210 by intradermal injection of antagomir-210 blocked the immune imbalance and the development of psoriasis-like inflammation in an imiquimod-induced or IL-23-induced psoriasis-like mouse model...
May 14, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29754330/gender-differences-in-axial-spondyloarthritis-women-are-not-so-lucky
#4
REVIEW
T Rusman, R F van Vollenhoven, I E van der Horst-Bruinsma
PURPOSE OF REVIEW: Ankylosing spondylitis (AS) was historically seen as a predominantly male disease. However, more recent data showed a more homogenous sex prevalence. Unfortunately, in many studies in axial spondyloarthritis (axSpA), the number of women included is low and the analyses are often not stratified for gender distribution. The purpose of this review is to aggregate the existing data on gender differences in axSpA in order to increase the awareness that female axSpA patients are still under-recognized...
May 12, 2018: Current Rheumatology Reports
https://www.readbyqxmd.com/read/29748971/association-between-serum-interleukin-17a-and-clinical-response-to-tofacitinib-and-etanercept-in-moderate-to-severe-psoriasis
#5
L Fitz, W Zhang, C Soderstrom, S Fraser, J Lee, A Quazi, R Wolk, C A Mebus, H Valdez, G Berstein
BACKGROUND: Psoriasis is a systemic inflammatory disease with a pathophysiology involving interleukin (IL)-17. Tofacitinib is an oral Janus kinase inhibitor. Etanercept is a tumour necrosis factor-α inhibitor used in the treatment of psoriasis. Neither agent inhibits IL-17 directly. AIM: To evaluate correlations between circulating IL-17A and clinical efficacy in patients with psoriasis treated with tofacitinib or etanercept. METHODS: Serum concentrations of IL-17A homodimer and IL-17A/F heterodimer were determined by immunoassays at weeks 0, 4 and 12 in patients with moderate to severe psoriasis treated with placebo (n = 60), tofacitinib 5 mg twice daily (n = 184), tofacitinib 10 mg twice daily (n = 190), or etanercept 50 mg subcutaneously twice weekly (n = 190)...
May 10, 2018: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/29748001/nfkb1-mediates-th1-th17-activation-in-the-pathogenesis-of-psoriasis
#6
Fusheng Zhou, Zhengwei Zhu, Jinping Gao, Chao Yang, Leilei Wen, Lu Liu, Xianbo Zuo, Xiaodong Zheng, Yinjuan Shi, Caihong Zhu, Bo Liang, Xianyong Yin, Wenjun Wang, Hui Cheng, Songke Shen, Xianfa Tang, Huayang Tang, Liangdan Sun, Anping Zhang, Sen Yang, Xuejun Zhang, Yujun Sheng
This study was aimed to investigate whether NFKB1 participates in the pathogenesis of psoriasis by mediating Th1/Th17 cells. In this study, expression of NFKB1 was assessed in skin tissues from psoriasis patients and the healthy controls through Western blot and Immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum levels of IFN-γ, IL-17 (IL-17A) and IL-17RA. The imiquimod-induced psoriasis mouse model was employed to examine the role of NFKB1 in psoriasis via the assessment of psoriasis area and severity index (PASI), including erythema, thickness and scales...
May 2, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29742185/the-role-of-il-17-in-the-human-immune-system-and-its-blockage-as-a-treatment-of-rheumatoid-arthritis-ankylosing-spondylitis-and-psoriatic-arthritis
#7
Juan J Jaller Char, Jose A Jaller, Jill S Waibel, Dhaval G Bhanusali, Neha Bhanusali
Interleukin 17 (IL-17) functions as a bridge between the innate and adaptive immunity. In addition to being a crucial defense mechanism against extracellular pathogens, it plays a significant role in inflammation, therefore considered a decisive factor in inflammatory conditions; hence the importance of its understanding for the treatment of autoimmune diseases. Animal models have demonstrated that blockage of the IL-17 receptor (IL-17R) may prevent these pathologies. For instance, there is evidence that IL-17R-deficient mice may be protected against the development of collagen-induced arthritis (CIA) and experimental autoimmune encephalitis (EAE)...
May 1, 2018: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29737896/systematic-review-of-anti-drug-antibodies-of-il-17-inhibitors-for-psoriasis
#8
Logan W Thomas, Erica B Lee, Jashin J Wu
Three main biologics target the IL-17 pathway; these include secukinmab, ixekizumab, brodalumab, all of which are approved for treatment of moderate-to-severe plaque psoriasis. We performed a systematic review of the literature to determine if IL-17 inhibitors are prone to developing ADA and how efficacy of treatment is influenced. A total of 14 papers were reviewed. Only one secukinmab trial detected treatment-emergent ADA in 4 out of 996 (0.41%) patients during the 52-week treatment period. Two of these patients (1 on 150-mg retreatment as needed and 1 on 150-mg fixed interval) were found to have neutralizing antibodies, however they were not associated with decreased efficacy...
May 8, 2018: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29737208/the-immunoregulatory-effects-of-traditional-chinese-medicine-on-psoriasis-via-its-action-on-interleukin-advances-and-considerations
#9
Minfeng Wu, Yu Deng, Su Li, Yu Chen, Dongjie Guo, Xingxiu Jin, Qi Xu, Bin Li, Fulun Li
Psoriasis is a chronic inflammatory cutaneous disease characterized by clinical manifestations of erythema and white scales. The pathogenesis of psoriasis is not yet clear. Despite a combination of hormonal therapy and physiotherapy used in Western medicine, the condition often relapses after withdrawal of drugs. Traditional Chinese medicine (TCM) has therapeutic features and may be a clinically effective formula by regulating unbalanced immune systems, such as by targeting interleukins. In this paper, we review recent research about how Chinese medicine immunoregulates psoriasis via interleukins, and systematically summarizes the related mechanisms...
May 8, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29729165/modern-specific-features-and-therapy-of-psoriasis-and-arthropathic-psoriasis-courses
#10
Orysya O Syzon, Marianna O Dashko, Ulyana V Fedorova
OBJECTIVE: Introduction:Psoriasis affects about 2% of population. In 30-40% of occurrences arthropathic psoriasis (AP) is diagnosed and it leads to 11-19% of disability cases development. Recent studies have shown that psoriasis is often synergistically combined with herpesvirus of the 1st and 2nd type, which, according to many scientists, determines the severity, frequency of recurrences, and the course of this dermatosis. Recently, new biomarkers, i.e. a system of small ribonucleic microRNA acids, have been described...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29718027/emerging-therapies-in-psoriasis-a-systematic-review
#11
Erica B Lee, Mina Amin, Tina Bhutani, Jashin J Wu
Many new biologics are being studied for use in psoriasis. In this review, we evaluate and summarize findings about emerging biologic therapies for psoriasis. We reviewed published data from phase 2 and 3 clinical trials of 2 IL-17 inhibitors (ixekizumab and brodalumab); 3 IL-23 inhibitors (guselkumab, tildrakizumab, and risankizumab); and 1 tumor necrosis factor (TNF) inhibitor (certolizumab pegol). Janus kinase inhibitors were not included in our review, as they currently are not approved by the US Food and Drug Administration (FDA) and there are no plans to further develop this class for treatment of psoriasis...
March 2018: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/29691866/gold-lotion-from-citrus-peel-extract-ameliorates-imiquimod-induced-psoriasis-like-dermatitis-in-murine
#12
Chi-Chien Lin, Jung-Ju Wu, Yi-Gen Pan, Ya-Hsuan Chao, Fang-Chu Lin, Ying-Ray Lee, Ching-Liang Chu
BACKGROUND: A natural mixed product Gold lotion (GL), which is made from the peels of six citrus fruits, has recently been identified to possess anti-oxidative, anti-inflammatory, and immunomodulatory effects. GL has been used to protect skin against UV-induced damage, but the activity to psoriasis, a chronic autoimmune skin disease caused by dysregulation between immune cells and keratinocytes, is not known. Thus, we evaluated the effect of GL on imiquimod (IMQ)-induced psoriasis-like inflammation in mice...
April 24, 2018: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/29689250/card14-gain-of-function-mutation-alone-is-sufficient-to-drive-il-23-il-17-mediated-psoriasiform-skin-inflammation-in-vivo
#13
Mark Mellett, Barbara Meier, Deepa Mohanan, Rebekka Schairer, Phil Cheng, Takashi K Satoh, Betina Kiefer, Caroline Ospelt, Stephan Nobbe, Margot Thome, Emmanuel Contassot, Lars E French
Rare autosomal dominant mutations in the gene encoding the keratinocyte signaling molecule, Caspase Recruitment Domain-Containing Protein 14 (CARD14), have been associated with an increased susceptibility to psoriasis but the physiological impact of CARD14 gain-of-function mutations remains to be fully determined in vivo. Here, we report that heterozygous mice harboring a CARD14 gain-of-function mutation (Card14ΔE138) spontaneously develop a chronic psoriatic phenotype with characteristic scaling skin lesions, epidermal thickening, keratinocyte hyperproliferation, hyperkeratosis and immune cell infiltration...
April 21, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29686529/notch1-signaling-regulates-the-th17-treg-immune-imbalance-in-patients-with-psoriasis-vulgaris
#14
Lei Ma, HaiBo Xue, Tianqin Gao, MeiLan Gao, YuJie Zhang
Purpose: To evaluate the regulating effect of Notch1 signaling on Th17/Treg immune imbalance in psoriasis vulgaris (PV). Materials and Methods: Notch1, Hes-1, ROR γ t, Foxp3, IL-17, and IL-10 mRNA expression, as well as Th17 and Treg cell percentages in peripheral CD4+ T cells, were detected by real-time quantitative RT-PCR and flow cytometry, and serum concentrations of IL-17 and IL-10 were detected by ELISA in 36 PV patients and 32 healthy controls. Additionally, CD4+ T cells from 12 PV patients were treated with γ -secretase inhibitor DAPT, and the above indexes were measured...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29670287/electrophilic-properties-of-itaconate-and-derivatives-regulate-the-i%C3%AE%C2%BAb%C3%AE-atf3-inflammatory-axis
#15
Monika Bambouskova, Laurent Gorvel, Vicky Lampropoulou, Alexey Sergushichev, Ekaterina Loginicheva, Kendall Johnson, Daniel Korenfeld, Mary Elizabeth Mathyer, Hyeryun Kim, Li-Hao Huang, Dustin Duncan, Howard Bregman, Abdurrahman Keskin, Andrea Santeford, Rajendra S Apte, Raghav Sehgal, Britney Johnson, Gaya K Amarasinghe, Miguel P Soares, Takashi Satoh, Shizuo Akira, Tsonwin Hai, Cristina de Guzman Strong, Karine Auclair, Thomas P Roddy, Scott A Biller, Marko Jovanovic, Eynav Klechevsky, Kelly M Stewart, Gwendalyn J Randolph, Maxim N Artyomov
Metabolic regulation has been recognized as a powerful principle guiding immune responses. Inflammatory macrophages undergo extensive metabolic rewiring 1 marked by the production of substantial amounts of itaconate, which has recently been described as an immunoregulatory metabolite 2 . Itaconate and its membrane-permeable derivative dimethyl itaconate (DI) selectively inhibit a subset of cytokines 2 , including IL-6 and IL-12 but not TNF. The major effects of itaconate on cellular metabolism during macrophage activation have been attributed to the inhibition of succinate dehydrogenase2,3 , yet this inhibition alone is not sufficient to account for the pronounced immunoregulatory effects observed in the case of DI...
April 18, 2018: Nature
https://www.readbyqxmd.com/read/29660300/the-major-orphan-forms-of-ichthyosis-are-characterized-by-systemic-t-cell-activation-and-th-17-tc-17-th-22-tc22-polarization-in-blood
#16
Tali Czarnowicki, Helen He, Alexandra Leonard, Kunal Malik, Shai Magidi, Stephanie Rangel, Krishna Patel, Kara Ramsey, Morgan Murphrey, Teresa Song, Yeriel Estrada, Hue-Chi Wen, James G Krueger, Emma Guttman-Yassky, Amy S Paller
The ichthyoses are rare skin disorders with immune and barrier aberrations. Identifying blood phenotypes may advance targeted-therapeutics.We aimed to compare frequencies of skin homing/CLA+ vs. systemic/CLA- "polar" CD4+ /CD8+ and activated T-cell subsets in ichthyosis vs. atopic dermatitis/AD, psoriasis and control blood, with appropriate clinical correlations. Flow cytometry was used to measure IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines in CD4+ /CD8+ T-cells, with ICOS and HLA-DR defining mid- and long-term T-cell activation, respectively...
April 13, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29650963/epigenetic-control-of-il-23-expression-in-keratinocytes-is-important-for-chronic-skin-inflammation
#17
Hui Li, Qi Yao, Alberto Garcia Mariscal, Xudong Wu, Justus Hülse, Esben Pedersen, Kristian Helin, Ari Waisman, Caroline Vinkel, Simon Francis Thomsen, Alexandra Avgustinova, Salvador Aznar Benitah, Paola Lovato, Hanne Norsgaard, Mette Sidsel Mortensen, Lone Veng, Björn Rozell, Cord Brakebusch
The chronic skin inflammation psoriasis is crucially dependent on the IL-23/IL-17 cytokine axis. Although IL-23 is expressed by psoriatic keratinocytes and immune cells, only the immune cell-derived IL-23 is believed to be disease relevant. Here we use a genetic mouse model to show that keratinocyte-produced IL-23 is sufficient to cause a chronic skin inflammation with an IL-17 profile. Furthermore, we reveal a cell-autonomous nuclear function for the actin polymerizing molecule N-WASP, which controls IL-23 expression in keratinocytes by regulating the degradation of the histone methyltransferases G9a and GLP, and H3K9 dimethylation of the IL-23 promoter...
April 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29642409/squamous-cell-carcinoma-antigen-2-scca2-serpinb4-an-emerging-biomarker-for-skin-inflammatory-diseases
#18
REVIEW
Kenji Izuhara, Yukie Yamaguchi, Shoichiro Ohta, Satoshi Nunomura, Yasuhiro Nanri, Yoshinori Azuma, Noriko Nomura, Yasuhiko Noguchi, Michiko Aihara
Squamous cell carcinoma antigens 1 and 2 (SCCA1 and 2, SERPIN B3 and B4), members of the ovalbumin serpin (ov-serpin)/clade B serpin family, were originally discovered as tumor-specific antigens and are used as tumor markers for various kinds of squamous cell carcinomas. Recently, our understanding of the underlying mechanisms of how SCCA1/2 enhance tumor growth has greatly increased. Moreover, it has been shown that SCCA1/2 are involved in the pathogenesis of several inflammatory diseases: asthma, psoriasis, and atopic dermatitis (AD)...
April 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29624178/correlation-of-t-cell-and-il-17-cell-subsets-in-lesional-skin-of-different-subtypes-of-psoriasis
#19
Zhen-Rui Shi, Xi-Qing Li, Ru-Zeng Xue, Zeng-Qi Tang, Guo-Zhen Tan, Lin Zheng, Liangchun Wang
No abstract text is available yet for this article.
April 6, 2018: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/29615641/maresin-1-suppresses-imiquimod-induced-skin-inflammation-by-regulating-il-23-receptor-expression
#20
Natsuko Saito-Sasaki, Yu Sawada, Emi Mashima, Takashi Yamaguchi, Shun Ohmori, Haruna Yoshioka, Sanehito Haruyama, Etsuko Okada, Motonobu Nakamura
The anti-inflammatory effect of omega 3 polyunsaturated fatty acids has been confirmed in various inflammatory disease models. Maresin-1 (MaR1) is a lipid mediator derived from the omega-3 fatty acid docosahexaenoic acid (DHA) that has displayed strong anti-inflammatory effects in various inflammatory disease models. However, the effect of topical MaR1 on cutaneous inflammation remains unclear. Therefore, we initially examined the anti-inflammatory effects of topical Maresin-1 using an imiquimod (IMQ)-induced psoriasis-like mouse model of inflammation...
April 3, 2018: Scientific Reports
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