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il 17 inhibition

Tomasz Herjan, Lingzi Hong, Jodi Bubenik, Katarzyna Bulek, Wen Qian, Caini Liu, Xiao Li, Xing Chen, Hui Yang, Suidong Ouyang, Hao Zhou, Junjie Zhao, Kommireddy Vasu, Eric Cockman, Mark Aronica, Kewal Asosingh, Donny D Licatalosi, Jun Qin, Paul L Fox, Thomas A Hamilton, Donna Driscoll, Xiaoxia Li
Mechanisms that degrade inflammatory mRNAs are well known; however, stabilizing mechanisms are poorly understood. Here, we show that Act1, an interleukin-17 (IL-17)-receptor-complex adaptor, binds and stabilizes mRNAs encoding key inflammatory proteins. The Act1 SEFIR domain binds a stem-loop structure, the SEFIR-binding element (SBE), in the 3' untranslated region (UTR) of Cxcl1 mRNA, encoding an inflammatory chemokine. mRNA-bound Act1 directs formation of three compartmentally distinct RNA-protein complexes (RNPs) that regulate three disparate events in inflammatory-mRNA metabolism: preventing mRNA decay in the nucleus, inhibiting mRNA decapping in P bodies and promoting translation...
April 2018: Nature Immunology
Moslem Ahmadi, Fateme Sadri-Ardalani, Mohammad M Amiri, Mahmood Jeddi-Tehrani, Mahdi Shabani, Fazel Shokri
AIM: We investigated cellular and protective immune responses in mice vaccinated with recombinant HER2 extracellular subdomains. MATERIALS & METHODS: Balb/C mice were immunized with recombinant full HER2 extracellular domain and subdomain proteins. Humoral and cellular immune response and antitumor effect was evaluated using a syngeneic mice tumor model. RESULTS: All recombinant proteins induced secretion of IL-4 and particularly IFN-γ and IL-17 cytokines...
March 1, 2018: Immunotherapy
Gerd Meyer Zu Horste, Dariusz Przybylski, Markus A Schramm, Chao Wang, Alexandra Schnell, Youjin Lee, Raymond Sobel, Aviv Regev, Vijay K Kuchroo
The death receptor Fas removes activated lymphocytes through apoptosis. Previous transcriptional profiling predicted that Fas positively regulates interleukin-17 (IL-17)-producing T helper 17 (Th17) cells. Here, we demonstrate that Fas promoted the generation and stability of Th17 cells and prevented their differentiation into Th1 cells. Mice with T-cell- and Th17-cell-specific deletion of Fas were protected from induced autoimmunity, and Th17 cell differentiation and stability were impaired. Fas-deficient Th17 cells instead developed a Th1-cell-like transcriptional profile, which a new algorithm predicted to depend on STAT1...
March 20, 2018: Immunity
Nicolas Gourdin, Marion Bossennec, Céline Rodriguez, Selena Vigano, Christelle Machon, Camilla Jandus, David Bauché, Julien Faget, Isabelle Durand, Nicolas Chopin, Olivier Tredan, Julien C Marie, Bertrand Dubois, Jérôme Guitton, Pedro Romero, Christophe Caux, Christine Ménétrier-Caux
The production of CD73-derived Adenosine (Ado) by Tregs, has been proposed as a resistance mechanism to anti-PD1 therapy in murine tumor models. We reported that Human Tregs express the ecto-nucleotidase CD39, that generates AMP from ATP, but do not express the AMPase CD73. In contrast, CD73 defined a subset of effector CD4+ T cells (Teffs), enriched in polyfunctional Th1.17 cells characterized by expression of CXCR3, CCR6 and MDR1 and production of IL-17A/IFN-γ/IL-22/GM-CSF. CD39+ Tregs selectively targeted CD73+ Teffs through cooperative degradation of ATP into Ado inhibiting and restricting the ability of CD73+ Teffs to secrete IL-17A...
March 20, 2018: Cancer Research
Bram Verstockt, Marc Ferrante, Séverine Vermeire, Gert Van Assche
The advent of anti-TNF agents has dramatically changed the treatment algorithms for IBD in the last 15 years, but primarily and more importantly secondary loss of response is often observed. Fortunately , new treatment options have been actively explored and some have already entered our clinical practice. In the class of anti-cytokine agents, the anti-IL12/IL23 monoclonal antibodies (mAbs) have entered clinical practice with the anti-p40 mAb ustekinumab in Crohn's disease (CD). Also, more selective anti-IL23 agents (anti-p19) have shown efficacy and are being further developed, in contrast to agents inhibiting IL-17 downstream which have failed in clinical trials despite their clear efficacy in psoriasis (Verstockt et al...
March 19, 2018: Journal of Gastroenterology
Li Huang, Meijuan Wang, Yongdong Yan, Wenjing Gu, Xinxing Zhang, Jiahong Tan, Huiming Sun, Wei Ji, Zhengrong Chen
BACKGROUND: The aim of this study was to investigate the mechanisms of OX40L in regulating helper T (Th) cells differentiation through phosphoinositide 3-kinase (PI3K)/AKT and p38 mitogen-activated protein kinase signaling pathway in vitro and in vivo experiments. METHODS: Serum samples of patients with asthma and healthy controls were used to explore the association between OX40L and Th cells. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum concentrations of OX40L, IL-4, IFN-γ, IL-17 and TGF-β...
March 20, 2018: Journal of Translational Medicine
Linlin Dong, Xiaoyu Zheng, Kun Wang, Guonian Wang, Huichao Zou
BACKGROUND: The T-helper 17 (Th17)/regulatory T (Treg) balance is essential for immune homeostasis. But the effects of gastric surgery on this balance remain unclear. The aim of present study is to identify the influence of gastric surgery on Th17/Treg balance and the role of programmed death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway in this process. METHODS: Mice were divided into Control, Sham and Surgery group randomly. Animals in Surgery group accepted partial gastrectomy...
March 16, 2018: Journal of Trauma and Acute Care Surgery
Peng You, Ning Chen, Lin Su, Tao Peng, Guodong Chen, Yulan Liu
Transforming growth factor β1 (TGF-β1) has a crucial role in regulating the balance of type 17 T-helper cells (Th17) and T regulatory cells (Tregs) that are involved in the pathogenesis of inflammatory bowel disease, while the function of local TGF-β1 in this process has remained to be fully elucidated. The present study investigated the effects of different local TGF-β1 levels on the Treg/Th17 balance and on the dexamethasone efficacy in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis...
April 2018: Experimental and Therapeutic Medicine
Ji Yang, Xue Yang, Jie Yang, Ming Li
OBJECTIVE: Hydroxychloroquine (HCQ) is a commonly used medicine for the treatment of systemic lupus erythematosus (SLE), and Th17 cells are closely related to the pathogenesis of SLE. However, the role and mechanism of HCQ on Th17 cell differentiation in SLE is not clearly understood. Here, we investigate the effect of HCQ on Th17 cell differentiation both in vitro and in patients with SLE. METHODS: Twenty-five patients with SLE were divided into 2 treatment groups: prednisone alone and HCQ plus prednisone...
March 15, 2018: Journal of Rheumatology
Zimu Zhang, Zhenyi Xue, Ying Liu, Hongkun Liu, Xiangdong Guo, Yan Li, Hongwei Yang, Lijuan Zhang, Yurong Da, Zhi Yao, Rongxin Zhang
Among T helper (Th) cell subsets differentiated from naive CD4+ T cells, IL-17-producing Th17 cells are closely associated with the pathogenesis of autoimmune diseases, including multiple sclerosis (MS) and the MS animal model, experimental autoimmune encephalomyelitis (EAE). The modulation of Th17 differentiation offers a potential avenue for treatment. Although a series of microRNAs (miRNAs) that modulate autoimmune disease development have been reported, further studies on miRNA roles in Th17 differentiation and MS pathogenesis are still warranted...
March 12, 2018: Brain, Behavior, and Immunity
Cheol-Jung Lee, Su-Jin Moon, Jeong-Hee Jeong, Sangbae Lee, Mee-Hyun Lee, Sun-Mi Yoo, Hye Suk Lee, Han Chang Kang, Joo Young Lee, Weon Sun Lee, Hee-Jin Lee, Eun-Kyung Kim, Joo-Yeon Jhun, Mi-La Cho, Jun-Ki Min, Yong-Yeon Cho
Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the synovial joints. Although involvement of the fibroblast growth factor (FGF) signaling pathway has been suggested as an important modulator in RA development, no clear evidence has been provided. In this study, we found that synovial fluid basic FGF (bFGF) concentration was significantly higher in RA than in osteoarthritis (OA) patients. bFGF stimulates proliferation and migration of human fibroblast-like synoviocytes (FLSs) by activation of the bFGF-FGF receptor 3 (FGFR3)-ribosomal S6 kinase 2 (RSK2) signaling axis...
March 14, 2018: Cell Death & Disease
Wei Liu, Yufeng Sun, Zhenping Cheng, Yong Guo, Peiming Liu, Ying Wen
CONTEXT: Rheumatoid arthritis (RA) is a common systemic auto-immune disease, which is characterized by chronic and symmetry synovial inflammation. Crocin has been reported to exhibit anti-inflammatory effects in animal models. OBJECTIVE: This study investigates the anti-inflammatory and anti-arthritic effects of crocin on type II collagen-induced arthritis (CIA) in Wistar rats. MATERIALS AND METHODS: The CIA rat model was established and randomly divided into five groups with or without crocin treatment (10, 20 or 40 mg/kg), which was started on day 21 after arthritis induction and persisted for 36 days...
December 2018: Pharmaceutical Biology
Tingting Zheng, Weiheng Zhao, Hongjin Li, Shuxiu Xiao, Ran Hu, Miaomiao Han, Heng Liu, Yeqiang Liu, Kinya Otsu, Xinguang Liu, Gonghua Huang
Dendritic cells (DCs) contribute to psoriasis pathogenesis. In a mouse model of imiquimod-induced psoriasiform skin inflammation, we found that p38α activity in Langerhans cells (LCs), a skin-resident subset of DCs, promoted the generation of T cells that produce IL-17, a proinflammatory cytokine that is implicated in autoimmune disease. Deletion of p38α in LCs, but not in other skin or circulating DC subsets or T cells, decreased T cell-mediated psoriasiform skin inflammation in mice. The activity of p38α in LCs specifically promoted IL-17 production from γδ and CD4+ T cells by increasing the abundance of IL-23 and IL-6, two cytokines that stimulate IL-17 secretion...
March 13, 2018: Science Signaling
Xiao-Yu Yu, Fei Fu, Wen-Na Kong, Qian-Kun Xuan, Dong-Hua Wen, Xiao-Qing Chen, Yong-Ming He, Li-Hua He, Jian Guo, Ai-Ping Zhou, Yang-Hong Xi, Li-Jun Ni, Yu-Feng Yao, Wen-Juan Wu
Streptococcus agalactiae and Candida albicans often co-colonize the female genital tract, and under certain conditions induce mucosal inflammation. The role of the interaction between the two organisms in candidal vaginitis is not known. In this study, we found that co-infection with S. agalactiae significantly attenuated the hyphal development of C. albicans , and that EFG1 -Hwp1 signal pathway of C. albicans was involved in this process. In a mouse model of vulvovaginal candidiasis (VVC), the fungal burden and the levels of pro-inflammatory cytokines, IL-1β, IL-6 and TNF-α showed a increase on co-infection with S...
2018: Frontiers in Microbiology
Vida Sheikh, Pinar Kasapoglu, Alireza Zamani, Zahra Basiri, Ahmad Tahamoli-Roudsari, Mahdi Alahgholi-Hajibehzad
1 α, 25-dihydroxyvitamin D3 (VitD3) has been suggested to have strong modulatory properties in the immune system. Researchers in the present study primarily aimed to understand the effect of VitD3 on human CD4+ T cell proliferation in antigen presenting cells (APCs) free condition in vitro. The effect of VitD3 on intracellular cytokine responses trend to Th1, Th2, Th17 and Th22 was evaluated using the flow cytometry. Moreover the effect of VitD3 on the expression of inhibitory markers such as PD1, PD-L1, and CTLA4 which are induced upon polyclonal T cell receptor (TCR) activation on CD4+ T cells, was assessed...
March 6, 2018: Human Immunology
Mei Jin, Wei Zhou, Chunshi Jin, Zhe Jiang, Shengbao Diao, Zhehu Jin, Gao Li
Twenty-seven compounds including nine triterpenoids (1-9), eight sterols (10-17), two ribonucleotides (18, 19), four phenols (20-23), three glycosides (24-26), and one furan (27) were isolated from the fruiting bodies of Trametes versicolor (L.) Lloyd. This study is the first confirmation of the presence of the 11 compounds (3, 5, 6, 8, 18, 20, 21, 23-25, and 27) isolated from the Polyporaceae family, with six of these (2 and 12-16) from the genus Trametes. Compounds 3, 4, 10, 11, 16 and 17 were found to significantly inhibit the production of NO, TNF-α and IL-6 in a dose-dependent manner...
March 9, 2018: Natural Product Research
Mei Liu, Xiaotian Zhou, Lin Zhou, Zhenzhou Liu, Jinbo Yuan, Jianwen Cheng, Jinmin Zhao, Longfei Wu, Hui Li, Haiwen Qiu, Jiake Xu
The discovery of new therapeutic drugs with the ability of preventing inflammation and joint destruction with less adverse effects is urgently needed for rheumatoid arthritis (RA). Carnosic acid (CA), a major phenolic compound isolated from the leaves of Rosemary (Rosmarinus officinalis L.), has been reported to have antioxidative and antimicrobial properties. However, its effects on RA have not been elucidated. Here, we investigated the effects of CA on osteoclasts and fibroblast-like synoviocytes in vitro and on collagen-induced arthritis (CIA) in Wistar rats in vivo...
March 9, 2018: Journal of Cellular Physiology
F F Wang, Y Wang, L Wang, T S Wang, Y P Bai
BACKGROUND: T-cell immunoglobulin and ITIM domain (TIGIT), a co-inhibitory receptor, suppresses CD4+ T-cell responses by triggering CD155. TIGIT shifts the balance of cytokines, including interferon (IFN)-γ, interleukin (IL)-10 and IL-17A, and affects the proliferation of CD4+ T cells. AIM: To investigate TIGIT expression and its effects on CD4+ T-cell function in psoriasis. METHODS: In total, 28 patients with psoriasis vulgaris PV and 14 healthy controls (HCs) were enrolled...
March 7, 2018: Clinical and Experimental Dermatology
Weijie Zhong, Xin Xu, Zhigang Zhu, Li Yang, Hong Du, Zhongjun Xia, Zhaohu Yuan, Huabao Xiong, Qinghua Du, Yaming Wei, Qingshan Li
Rituximab resistance has become increasingly common in patients with diffuse large B cell lymphoma (DLBCL). However, the mechanisms involved remain unclear. In this study, we aimed to examine the effect of rituximab on interleukin (IL)-17A and to investigate the role of IL-17A in rituximab resistance and its prognostic value in patients with DLBCL. Our retrospective analysis revealed that rituximab increased IL-6 expression levels in patients with DLBCL, and the increased IL-6 levels in turn induced the differentiation of Th17 and IL-17+Foxp3+ Treg cells, which secreted IL-17A both in vivo and in vitro...
March 5, 2018: International Journal of Oncology
Qin Zhu, Peifen Zheng, Xinyu Chen, Feng Zhou, Qiaona He, Yuefeng Yang
Ulcerative colitis (UC) is a chronic and nonspecific intestinal inflammatory disease, which may increase the risk of colon cancer. Andrographolide is a main active component of Andrographis paniculata . The anti-inflammatory ability of andrographolide suggested its potential therapeutic effect against UC. In the present study, elevated serum concentrations of proinflammatory factors, including (TNF)-α, interleukin (IL)-1β, IL-6 and IL-23, as well as increased percentages of Th17 cells (IL-17+CD4+ cells) in CD4+ cells were detected in UC patients compared to that in healthy donors...
2018: American Journal of Translational Research
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