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https://www.readbyqxmd.com/read/28100093/p19-targeted-abd-derived-protein-variants-inhibit-il-23-binding-and-exert-suppressive-control-over-il-23-stimulated-expansion-of-primary-human-il-17-t-cells
#1
Lucie Křížová, Milan Kuchař, Hana Petroková, Radim Osička, Marie Hlavničková, Ondřej Pelák, Jiří Černý, Tomáš Kalina, Petr Malý
Interleukin-23 (IL-23), a heterodimeric cytokine of covalently bound p19 and p40 proteins, has recently been closely associated with development of several chronic autoimmune diseases such as psoriasis, psoriatic arthritis or inflammatory bowel disease. Released by activated dendritic cells, IL-23 interacts with IL-23 receptor (IL-23R) on Th17 cells, thus promoting intracellular signaling, a pivotal step in Th17-driven pro-inflammatory axis. Here, we aimed to block the binding of IL-23 cytokine to its cell-surface receptor by novel inhibitory protein binders targeted to the p19 subunit of human IL-23...
January 19, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28099816/new-treatment-options-and-emerging-drugs-for-axial-spondyloarthritis-biological-and-targeted-synthetic-agents
#2
Eric Toussirot
Ankylosing spondylitis (AS) and axial spondyloarthritis (ax SpA) are chronic inflammatory diseases mainly involving the axial skeleton. Pharmacological treatments for AS and ax SpA usually include local glucocorticoid injections, NSAIDs and anti-TNFa agents. Since around 30% to 40% of patients are non responders or intolerant to anti-TNFa agents, we need new therapeutic options for AS and ax SpA. Areas covered: This review describes the new biological agents that can be used or are in development for AS or ax SpA as well as emerging synthetic targeted drugs...
January 18, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28096316/bay-11-7082-inhibits-the-nf-kb-and-nlrp3-inflammasome-pathways-and-protects-against-imq-induced-psoriasis
#3
Natasha Irrera, Mario Vaccaro, Alessandra Bitto, Giovanni Pallio, Gabriele Pizzino, Maria Lentini, Vincenzo Arcoraci, Letteria Minutoli, Michele Scuruchi, Giuseppina Cutroneo, Giuseppe Pio Anastasi, Roberta Ettari, Francesco Squadrito, Domenica Altavilla
BAY 11-7082 antagonizes I-κB kinase-β preventing nuclear translocation of NF-κB; it also inhibits NLRP3 inflammasome activation.NF-κB is involved in psoriasis, while the role of NLRP3 is controversial. We investigated BAY 11-7082 effects in an experimental model of psoriasis-like dermatitis. Psoriasis-like lesions were induced by a topical application of imiquimod cream (IMQ; 62.5 mg/day) on the shaved back skin of C57BL/6 and NLRP3 knock-out mice for 7 consecutive days. Sham psoriasis animals were challenged with vaseline cream...
January 17, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28096232/pr-957-a-selective-inhibitor-of-immunoproteasome-subunit-low-mw-polypeptide-7-attenuates-experimental-autoimmune-neuritis-by-suppressing-th17-cell-differentiation-and-regulating-cytokine-production
#4
Haijie Liu, Chunxiao Wan, Yanan Ding, Ranran Han, Yating He, Jinting Xiao, Junwei Hao
Experimental autoimmune neuritis (EAN) is a CD4(+) T cell-mediated autoimmune inflammatory demyelinating disease of the peripheral nervous system. It has been replicated in an animal model of human inflammatory demyelinating polyradiculoneuropathy, Guillain-Barré syndrome. In this study, we evaluated the therapeutic efficacy of a selective inhibitor of the immunoproteasome subunit, low-MW polypeptide 7 (PR-957) in rats with EAN. Our results showed that PR-957 significantly delayed onset day, reduced severity and shortened duration of EAN, and alleviated demyelination and inflammatory infiltration in sciatic nerves...
January 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28095479/central-role-of-il-23-and-il-17-producing-eosinophils-as-immunomodulatory-effector-cells-in-acute-pulmonary-aspergillosis-and-allergic-asthma
#5
Evelyn Santos Guerra, Chrono K Lee, Charles A Specht, Bhawna Yadav, Haibin Huang, Ali Akalin, Jun R Huh, Christian Mueller, Stuart M Levitz
Aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. We studied the contribution of lung eosinophils to these fungal diseases. By in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of IL-23 and IL-17. Remarkably, mice lacking eosinophils had a >95% reduction in the percentage of lung IL-23p19+ cells as well as markedly reduced IL-23 heterodimer in lung lavage fluid. Eosinophils killed A...
January 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28092402/%C3%AE-%C3%AE-t-cells-are-indispensable-for-il-23-mediated-protection-against-cona-induced-hepatitis-in-hepatitis-b-virus-transgenic-mice
#6
Ziyu Meng, Jingya Wang, Yifang Yuan, Guangchao Cao, Shuobing Fan, Chao Gao, Li Wang, Zheng Li, Xiaoli Wu, Zhenzhou Wu, Liqing Zhao, Zhinan Yin
Hepatitis B virus surface antigen (HBsAg) carriers are highly susceptible to liver injury triggered by environmental biochemical stimulation. Previously, we have reported an inverse correlation between γδT cells and liver damage in patients with HBV. However, whether γδT cells play a role in regulating the hypersensitivity of HBsAg carriers to biochemical stimulation-induced hepatitis is unknown. In this study, using hepatitis B virus transgenic (HBs-Tg) and HBs-Tg-TCRδ(-/-) mice, we found that mice genetically deficient in γδT cells exhibited more severe liver damage upon ConcanavalinA (ConA) treatment, as indicated by substantially higher serum alanine aminotransferase (ALT) levels, further elevated IFN-γ levels and more extensive necrosis...
January 16, 2017: Immunology
https://www.readbyqxmd.com/read/28088612/alterations-in-cytokine-gene-expression-profile-in-colon-mucosa-of-inflammatory-bowel-disease-patients-on-different-therapeutic-regimens
#7
Tsvetelina Velikova, Dobroslav Kyurkchiev, Zoya Spassova, Iliya Karakolev, Ekaterina Ivanova-Todorova, Iskra Altankova, Spaska Stanilova
Inflammatory bowel disease (IBD) is assumed to be caused by genetic and environmental factors that interact together in promoting intestinal immune dysregulation where cytokines have validated role. However, the underlying intimate mechanisms in the human IBD involving cytokines still needs to be supplemented especially in the clinical context. The aim of this study was to investigate the expression of some inflammatory and regulatory cytokines (IL-17A, IL-23, IL-6, TGFβ1, and IL-10) as well as of the transcription factor FoxP3 in mucosal samples of IBD and non-IBD patients...
January 12, 2017: Cytokine
https://www.readbyqxmd.com/read/28087506/a-randomised-phase-ii-study-evaluating-the-efficacy-and-safety-of-subcutaneously-administered-ustekinumab-and-guselkumab-in-patients-with-active-rheumatoid-arthritis-despite-treatment-with-methotrexate
#8
Josef S Smolen, Sandeep K Agarwal, Elena Ilivanova, Xie Lillian Xu, Ye Miao, Yanli Zhuang, Ivo Nnane, Waldemar Radziszewski, Andrew Greenspan, Anna Beutler, Daniel Baker
OBJECTIVE: Interleukin (IL)-12 and IL-23 have been implicated in the pathogenesis of rheumatoid arthritis (RA). The safety and efficacy of ustekinumab, a human monoclonal anti-IL-12/23 p40 antibody, and guselkumab, a human monoclonal anti-IL-23 antibody, were evaluated in adults with active RA despite methotrexate (MTX) therapy. METHODS: Patients were randomly assigned (1:1:1:1:1) to receive placebo at weeks 0, 4 and every 8 weeks (n=55), ustekinumab 90 mg at weeks 0, 4 and every 8 weeks (n=55), ustekinumab 90 mg at weeks 0, 4 and every 12 weeks (n=55), guselkumab 50 mg at weeks 0, 4 and every 8 weeks (n=55), or guselkumab 200 mg at weeks 0, 4 and every 8 weeks (n=54) through week 28; all patients continued a stable dose of MTX (10-25 mg/week)...
January 13, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28075473/spirulina-lipopolysaccharides-inhibit-tumor-growth-in-a-toll-like-receptor-4-dependent-manner-by-altering-the-cytokine-milieu-from-interleukin-17-interleukin-23-to-interferon-%C3%AE
#9
Hiromi Okuyama, Akira Tominaga, Satoshi Fukuoka, Takahiro Taguchi, Yutaka Kusumoto, Shiro Ono
Th17 cells and the cytokine they produce, interleukin (IL)-17, play an important role in tumor progression in humans and in mice. IL-6 and IL-23 are critical cytokines for the differentiation and propagation of Th17 cells, respectively. Bacterial lipopolysaccharides (LPS) are known to stimulate immune cells to produce such inflammatory cytokines. Contrary to Escherichia coli (E. coli) LPS, LPS from Spirulina has low toxicity and barely induces in vivo production of IL-6 and IL-23 in mice. We examined the antitumor effects of Spirulina LPS compared to E...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28074676/potential-route-of-th17-treg-cell-dynamics-in-targeting-type-1-diabetes-and-rheumatoid-arthritis-an-autoimmune-disorder-perspective
#10
Suresh Kumar Karri, A Sheela
Cytokines, small secreted proteins, have a specific effect on the interactions and communications between cells. They play a pivotal role in the pathogenesis of autoimmune diseases. Factors in the breakdown of self-tolerance and the subsequent events leading to the induction of pathogenic responses remain unclear for most of the autoimmune diseases. Large numbers of studies have revealed a general scheme in which pro-inflammatory cytokines contribute to the initiation and propagation of autoimmune inflammation, whereas anti-inflammatory cytokines facilitate the regression of inflammation and thereby recovery from the disease...
January 11, 2017: British Journal of Biomedical Science
https://www.readbyqxmd.com/read/28067223/the-microbiota-maintain-homeostasis-of-liver-resident-%C3%AE-%C3%AE-t-17-cells-in-a-lipid-antigen-cd1d-dependent-manner
#11
Fenglei Li, Xiaolei Hao, Yongyan Chen, Li Bai, Xiang Gao, Zhexiong Lian, Haiming Wei, Rui Sun, Zhigang Tian
The microbiota control regional immunity using mechanisms such as inducing IL-17A-producing γδ T (γδT-17) cells in various tissues. However, little is known regarding hepatic γδT cells that are constantly stimulated by gut commensal microbes. Here we show hepatic γδT cells are liver-resident cells and predominant producers of IL-17A. The microbiota sustain hepatic γδT-17 cell homeostasis, including activation, survival and proliferation. The global commensal quantity affects the number of liver-resident γδT-17 cells; indeed, E...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28067059/il-23-blockade-for-crohn-s-disease-next-generation-of-anti-cytokine-therapy
#12
Federica Furfaro, Daniela Gilardi, Mariangela Allocca, Clelia Cicerone, Carmen Correale, Gionata Fiorino, Silvio Danese
Adaptive immunity in intestinal inflammation may play a key role in the pathogenesis of Crohn's disease. In particular, interleukin (IL)-23 may be a key mediator in chronic intestinal inflammation by inducing the differentiation of naïve CD4+ T cells into Th17, with the production of several pro-inflammatory cytokines. Furthermore, IL-23 induces interferon-γ (IFN- γ) production from activated T cells, a critical cytokine in innate and adaptive immunity against infections. Areas covered: We aim to review the available data from literature regarding the role of IL-23, with a more specific focus on the recent progresses in the therapeutic modulation of this cytokine...
January 9, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28065580/fatigue-favors-in-vitro-th1-and-th17-like-cell-expansion-and-reduces-corticoid-sensitivity-in-ms-patients
#13
Hélcio Alvarenga-Filho, Marisa Salles, Joana Hygino, Thais B Ferreira, Priscila M Sacramento, Clarice Monteiro, Claudia Cristina F Vasconcelos, Regina Maria Papais Alvarenga, Cleonice A M Bento
Fatigue is a common "ghost" symptom in patients with multiple sclerosis (MS), an autoimmune disease mediated by T cells that target myelin antigens of the central nervous system. As fatigue has been associated with inflammatory states, its occurrence may negatively impact MS progression. The aim of this study was to evaluate the impact of fatigue on the cytokine profile of patients with relapsing-remitting (RR) MS. For our study, blood were collected from MS patients in clinical remission phase with (n=15) and without (n=15) fatigue...
December 30, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28061755/high-serum-resistin-associates-with-intrahepatic-inflammation-and-necrosis-an-index-of-disease-severity-for-patients-with-chronic-hbv-infection
#14
Zhongji Meng, Yonghong Zhang, Zhiqiang Wei, Ping Liu, Jian Kang, Yinhua Zhang, Deqiang Ma, Changzheng Ke, Yue Chen, Jie Luo, Zuojiong Gong
BACKGROUND: Studies have revealed that resistin plays a role as an intrahepatic cytokine with proinflammatory activities. This study investigated the association between serum resistin and fibrosis severity and the possible marker role of resistin in the inflammatory process of chronic hepatitis B. METHODS: In this study, 234 subjects with HBV infection were retrospectively selected, including 85 patients with chronic hepatitis B (CHB), 70 patients with HBV-related liver cirrhosis (LC-B), and 79 patients with HBV-related liver failure (LF-B)...
January 7, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28041935/role-of-interleukin-23-in-monocyte-derived-dendritic-cells-of-hbv-related-acute-on-chronic-liver-failure-and-its-correlation-with-the-severity-of-liver-damage
#15
Suxia Bao, Jianming Zheng, Ning Li, Chong Huang, Mingquan Chen, Qi Cheng, Qian Li, Qing Lu, Mengqi Zhu, Qingxia Ling, Kangkang Yu, Shengshen Chen, Guangfeng Shi
BACKGROUND: The role of interleukin-23 (IL-23) in monocyte-derived dendritic cells (MoDCs) from hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients remains unclear. The aim of this study was to observe the correlation between the activation of the IL-23 signaling pathway and the prognosis of HBV-ACLF patients. MATERIALS AND METHODS: The baseline levels of serum IL-6, IL-12, IL-17, IL-23, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) from immune tolerant (IT), chronic hepatitis B (CHB), HBV-ACLF patients and healthy individuals who served as healthy controls (HCs) were analyzed using the Luminex system, whereas serum IL-23 from HBV-ACLF patients was measured by ELISA before and after treatment...
December 29, 2016: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28035388/the-effect-of-inhaled-inactived-mycobacterium%C3%A2-phlei-as-a-treatment-for-asthma
#16
Moyu Ming, Chaoqian Li, Zhixi Luo, Shengqiu Lv, Qixiang Sun
Allergic asthma is a chronic airway disorder characterized by airway inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR). A murine model of asthma was used to examine the antiasthmatic effect of inhaled inactived Mycobacterium phlei (M. phlei). AHR, neutrophil levels, eosinophil levels and levels of interleukin (IL)‑17 and IL‑23 receptor (IL‑23R) were monitored. The results demonstrated that inactivated M. phlei alleviates the IL‑17+γδT cell‑mediated immune response and attenuates airway inflammation and airway hyperresponsiveness in the asthmatic murine lung, partially through inhibiting the expression of IL‑23R...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28035212/interleukin-17-expressing-innate-synovial-cells-drive-k-bxn-serum-induced-arthritis
#17
Wang Shik Cho, Eunkyeong Jang, Ho-Youn Kim, Jeehee Youn
K/BxN serum can induce arthritis in normal mice because of abundant autoantibodies that trigger an innate inflammatory response in joints. To determine whether IL-17 is involved in the pathogenesis of serum-induced arthritis, we injected wild-type and IL-17(-/-) mice with K/BxN serum and evaluated them for signs of arthritis. Unlike wild-type mice, IL-17(-/-) mice did not show any signs of arthritis. IL-17 was produced predominantly by CD3(-) CD4(-) γδTCR(-) NK1.1(-) Sca1(int) Thy1(hi) cells residing in the inflamed synovial tissue...
December 2016: Immune Network
https://www.readbyqxmd.com/read/28034757/vancomycin-pre-treatment-impairs-tissue-healing-in-experimental-colitis-importance-of-innate-lymphoid-cells
#18
Di Zhao, Chenwen Cai, Qing Zheng, Shuang Jin, Dongjuan Song, Jun Shen, Zhihua Ran
BACKGROUND AND AIMS: The interplay between luminal microbes and innate immunity during colonic epithelial repair has been well noted. At the same time, antibiotic has widely been used during flare-ups of ulcerative colitis. The possible effects of luminal microbiota disruption caused by antibiotics usage on epithelial repairing have been scarcely discussed. Innate lymphoid cells (ILCs) embedded in the lamina propria can be modulated by gut microbes, resulting in altered colonic IL-22/pSTAT3 levels, which is considered a prominent molecular axis in tissue repairing after epithelium damage...
December 27, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28033649/thrombospondin-derived-peptide-attenuates-sj%C3%A3-gren-s-syndrome-associated-ocular-surface-inflammation-in-mice
#19
Laura Contreras-Ruiz, Fayaz A Mir, Bruce Turpie, Sharmila Masli
Sjögren's syndrome is a second most common rheumatic disease in which autoimmune response targets exocrine glands (salivary and lacrimal glands) resulting in clinical symptoms of dry mouth and dry eye. Inflammation of the lacrimal gland induces tear abnormalities that contribute to the inflammation of the ocular surface, which includes ocular mucosa. Thrombospondin-1 (TSP-1) plays a critical regulatory role in the ocular mucosa and as such TSP-1-/- mice spontaneously develop chronic ocular surface inflammation associated with Sjögren's syndrome (SS)...
December 29, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28030850/changes-of-circulating-th22-cells-in-children-with-hand-foot-and-mouth-disease-caused-by-enterovirus-71-infection
#20
Dawei Cui, Fengyun Zhong, Jie Lin, Yidong Wu, Quan Long, Xianzhi Yang, Qiaoyun Zhu, Li Huang, Qifen Mao, Zhaoxia Huo, Zhe Zhou, Guoliang Xie, Shufa Zheng, Fei Yu, Yu Chen
Interleukin (IL)-22+CD4+T (Th22) cells play crucial roles in the pathogenesis of autoimmune diseases and infectious diseases, although the role of Th22 cells remains largely unclear in children with hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71). This study aims to explore the role of circulating IL-22+IL-17A-CD4+T (cTh22) cells in children with EV71-associated HFMD. We found that during the acute stage of illness, the frequencies of cTh22 and circulating IL-22+IL-17A+CD4+T (IL-22+cTh17) cells in CD4+T cells infrom affected patients, and especially in severely affected patients, were significantly higher than in healthy controls (HC)...
December 21, 2016: Oncotarget
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