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| 1 | Interleukin-33 drives hepatic fibrosis through activation of hepatic stellate cells显示文摘Liver fibrosis is a consequence of chronic liver disease,causing morbidity and mortality.Interleukin-33(IL-33)is a critical mediator of inflammation,which may be involved in the development of liver fibrosis.Here,we investigated the role of IL-33 in human patients and experimental bile-duct ligation(BDL)-induced fibrosis in mice.We report increased hepatic IL-33 expression in the murine BDL model of fibrosis and in surgical samples obtained from patients with liver fibrosis.Liver injury,inflammatory cell infiltration and fibrosis were reduced in the absence of the IL-33/ST2 receptor,and the activation of hepatic stellate cells(HSCs)was decreased in ST2-deficient mice.Recombinant IL-33 activated HSCs isolated from C57BL/6 mice,leading to the expression of IL-6,TGF-β,α-SMA and collagen,which was abrogated in the absence of ST2 or by pharmacological inhibition of MAPK signaling.Finally,administration of recombinant IL-33 significantly increased hepatic inflammation in sham-operated BL6 mice but did not enhance BDL-induced hepatic inflammation and fibrosis.In conclusion,BDL-induced liver inflammation and fibrosis are dependent on ST2 signaling in HSCs,and therefore,the IL-33/ST2 pathway may be a potential therapeutic target in human patients with chronic hepatitis and liver fibrosis. | Zhongming Tan Qianghui Liu Runqiu Jiang Long Lv Siamak S Shoto Isabelle Maillet Valerie Quesniaux Junwei Tang Wenjie Zhang Beicheng Sun Bernhard Ryffel | 2018 | Cellular & Molecular Immunology2018，15，4： | 24 |
| 2 | The development and function of follicular helper T cells in immune responses显示文摘小囊的助手 T 房间(Tfh ) 作为提供帮助让 B 房间增殖并且在幼芽的中心经历抗体亲密关系成熟的一个系被提交了。证据支持了那个 Tfh 子集开发象另外的系一样,依赖于一个特别 transcriptional 节目被开始的微型环境。它为 Tfh 房间的开发和函数作为主人管理者被看了那 Bcl-6 和 IL-21 行为。Tfh dysregulation 涉及自体免疫的病理的发展,例如全身的豺狼座 erythematosus,风湿性关节炎和另外的自体免疫的疾病。现在的评论在在他们的开发和函数的 Tfh 房间和焦点的域里加亮最近的进展。 | Maogen Chen Zhiyong Guo Weiqiang Ju Bernhard Ryffel Xiaoshun He Song Guo Zheng | 2012 | Cellular & Molecular Immunology2012，9，5： | 18 |
| 3 | Caspase-1 activation by NLRP3 inflammasome dampens IL-33-dependent house dust mite-induced allergic lung inflammation显示文摘The cysteine protease caspase-1(Casp-1)contributes to innate immunity through the assembly of NLRP3,NLRC4,AIM2,and NLRP6 inflammasomes.Here we ask whether caspase-1 activation plays a regulatory role in house dust mite(HDM)-induced experimental allergic airway inflammation.We report enhanced airway inflammation in caspase-1-deficient mice exposed toHDMwith a marked eosinophil recruitment,increased expression of IL-4,IL-5,IL-13,aswell as full-length and bioactive IL-33.Furthermore,mice deficient for NLRP3 failed to control eosinophil influx in the airways and displayed augmented Th2 cytokine and chemokine levels,suggesting that the NLPR3 inflammasome complex controls HDM-induced inflammation.IL-33 neutralization by administration of soluble ST2 receptor inhibited the enhanced allergic inflammation,while administration of recombinant IL-33 during challenge phase enhanced allergic inflammation in caspase-1-deficient mice.Therefore,we show that caspase-1,NLRP3,and ASC,but not NLRC4,contribute to the upregulation of allergic lung inflammation.Moreover,we cannot exclude an effect of caspase-11,because caspase-1-deficient mice are deficient for both caspases.Mechanistically,absence of caspase-1 is associated with increased expression of IL-33,uric acid,and spleen tyrosine kinase(Syk)production.This study highlights acritical role of caspase-1 activation andNLPR3/ASCinflammasomecomplex in the down-modulation of IL-33 in vivo and in vitro,thereby regulating Th2 response in HDM-induced allergic lung inflammation. | Fahima Madouri Noelline Guillou Louis Fauconnier Tiffany Marchiol Nathalie Rouxel Pauline Chenuet Aurelie Ledru Lionel Apetoh Franc¸ois Ghiringhelli Mathias Chamaillard Song Guo Zheng Fabrice Trovero Valerie F.J.Quesniaux Bernhard Ryffel Dieudonnee Togbe | 2015 | Journal of Molecular Cell Biology2015，7，4： | 8 |
| 4 | NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer显示文摘 | Couturier-Maillard Aurélie Secher Thomas Rehman Ateequr Normand Sylvain De Arcangelis Adéle Haesler Robert Huot Ludovic Grandjean Teddy Bressenot Aude Delanoye-Crespin Anne Gaillot Olivier Schreiber Stefan Lemoine Yves Ryffel Bernhard Hot D | 2013 | Journal of Clinical Investigation2013，，2： | 5 |
| 5 | Induced Foxp3^(+)regulatory T cells:a potential new weapon to treat autoimmune and inflammatory diseases?显示文摘Foxp3^(+)T regulatory cells(Tregs)consisting of natural and induced Treg subsets play a crucial role in the maintenance of immune homeostasis against self-antigen.The actions designed to correct defects in numbers or functions of Tregs may be therapeutic in the treatment of autoimmune diseases.While recent studies demonstrated that natural Tregs are instable and dysfunctional in the in-flammatory condition,induced Tregs(iTregs)may have a different feature.Here we review the progress of iTregs,particularly focus on their stability and function in the established autoimmune diseases.The advantage of iTregs as therapeutics used under inflammatory conditions is highlighted.Proper generation and manipulation of iTregs used for cellular therapy may provide a promise for the treatment of many autoimmune and inflammatory diseases. | Qin Lan Huimin Fan Valerie Quesniaux Bernhard Ryffel Zhongmin Liu Song Guo Zheng | 2012 | Journal of Molecular Cell Biology2012，4，1： | 3 |
| 6 | Phenotypic and functional characteristic of a newly dentified CDS+Foxp3-CDI03+ regulatory T cells显示文摘 | Ya Liu Qin Lan Ling Lu Maogen Chen Zanxian Xia Jilin Ma Julie Wang Huimin Fan Yi Shen Bernhard Ryffel David Brand Francisco Quismorio Zhongmin Liu David A. Horwitz Anping Xu Song Guo Zheng | 2014 | Journal of Molecular Cell Biology2014，8，1： | 2 |
| 7 | IL-17A Plays a Critical Role in the Pathogenesis of Liver Fibrosis through Hepatic Stellate Cell Activation显示文摘 | Zhongming Tan Xiaofeng Qian Runqiu Jiang Qianghui Liu Youjing Wang Chen Chen Xuehao Wang Bernhard Ryffel Beicheng Sun | 2013 | The Journal of Immunology2013，，4： | 2 |
| 8 | TUMOR NECROSIS FACTOR IS NOT ASSOCIATED WITH INTESTINAL ISCHEMIA/REPERFUSION-INDUCED LUNG INFLAMMATION显示文摘 | Alexandre Learth Soares Fernando Rodrigues Coelho Rodrigo Guabiraba Mamdouh Kamal B. Boris Vargaftig Lily Li Jian Li Wothan Tavares- de-Lima Bernhard Ryffel | 2010 | Shock2010，，3： | 2 |
| 9 | Adoptive Transfer of Human Gingiva‐Derived Mesenchymal Stem Cells Ameliorates Collagen‐Induced Arthritis via Suppression of Th1 and Th17 Cells and Enhancement of Regulatory T Cell Differentiation显示文摘 | Maogen Chen Wenru Su Xiaohong Lin Zhiyong Guo Julie Wang Qunzhou Zhang David Brand Bernhard Ryffel Jiefu Huang Zhongmin Liu Xiaoshun He Anh D. Le Song Guo Zheng | 2013 | Arthritis & Rheumatism2013，，5： | 1 |
| 10 | Histamine H2 Receptor Signaling in the Pathogenesis of Sepsis: Studies in a Murine Diabetes Model显示文摘 | Daniela Carlos Fernando Spiller Fabrício O. Souto Silvia C. Trevelin Vanessa F. Borges Andressa de Freitas José C. Alves-Filho Jo?o S. Silva Bernhard Ryffel Fernando Q. Cunha | 2013 | The Journal of Immunology2013，，3： | 1 |
| 11 | Interleukin-12: role of interferon-γ in IL-12 adverse effects显示文摘 | Ryffel Bernhard | 1997 | Clin Immunol Immunopathol1997，83，1： | 1 |
| 12 | Dengue virus infection: current concepts in immune mechanisms and lessons from murine models显示文摘 | Rodrigo Guabiraba Bernhard Ryffel | 2014 | Immunology2014，，2： | 1 |
| 13 | IL-17A Plays a Critical Role in the Pathogenesis of Liver Fibrosis through Hepatic Stellate Cell Activation显示文摘 | Zhongming Tan Xiaofeng Qian Runqiu Jiang Qianghui Liu Youjing Wang Chen Chen Xuehao Wang Bernhard Ryffel Beicheng Sun | 2013 | The Journal of Immunology2013，，4： | 1 |
| 14 | Inflammasome-IL-1-Th17 response in allergic lung inflammation显示文摘Allergic asthma has increased dramatically in prevalence and severity over the last three decades.Both clinical and experimental data support an important role of Th2 cell response in the allergic response.Recent investigations revealed that airway exposure to allergen in sensitized individuals causes the release of ATP and uric acid,activating the NLRP3 inflammasome complex and cleaving pro-IL-1b to mature IL-1b through caspase-1.The production of pro-IL-1b requires a toll-like receptor(TLR)4 signal which is provided by the allergen.IL-1b creates a pro-inflammatory milieu with the production of IL-6 and chemokines which mobilize neutrophils and enhance Th17 cell differentiation in the lung.Here,we review our results showing that NLRP3 inflammasome activation is required to develop allergic airway inflammation in mice and that IL-17 and IL-22 production by Th17 cells plays a critical role in established asthma.Therefore,inflammasome activation leading to IL-1b production contributes to the control of allergic asthma by enhancing Th17 cell differentiation. | Anne-Gaelle Besnard Dieudonnee Togbe Isabelle Couillin Zoming Tan Song Guo Zheng Francois Erard Marc Le Bert Valerie Quesniaux Bernhard Ryffel | 2012 | Journal of Molecular Cell Biology2012，4，1： | 0 |
| 15 | Safety of Human Recombinant Proteins显示文摘Recombinant human proteins play an important role in therapy, especially in stimulating the hematopoiesis after chemotherapy, e. g., erythropoietin and colony stimulating factors,while several promising candidates such as IL-6, IL-12, thrombopoietin and others are in clinical development. Since the recombinant proteins are copies of endogenous proteins, it was assumed that they would be well tolerated. While this assumption is correct for some, other proteins proved to be less well tolerated. Therefore, preclinical safety assessment of these pro teins is necessary. Based on the experience with several proteins, some guidance for the safety assessment can be given. Furthermore, data are presented demonstrating that preclinical toxi city studies may have a predictive value for man. Limitations of the classical approach of safety tests and new concepts are | BERNHARD RYFFEL (Institute of Pathology, University of Basel, CH-4031 Basel , Switzerland) ( Department of Immunology, Medical School Observatory 7925, University of Cape Town,South Africa.) | 1997 | Biomedical and Environmental Sciences1997，10，1： | 0 |
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