| 1 | 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 |
| 2 | Defensins couple dysbiosis to primary immunodeficiency in Crohn's disease显示文摘Antimicrobial peptides,including defensins,are essential effectors in host defence and in the maintenance of immune homeostasis.Clinical studies have linked the defective expression of both α-and β-defensin to the reduced killing of certain microorganisms by the intestinal mucosa of patients suffering from ileal and colonic Crohn's disease(CD),respectively.Only recently have the events leading to defective expression of defensins in CD been further elucidated,and are discussed herein.These events may account for CD-associated alterations in the microbiome and may subsequently precipitate the development of granulomatous inflammatory lesions in genetically-predisposed patients.We also address how these discoveries may pave the way for the development of a molecular medicine aimed at restoring gut barrier function in CD. | Mathias Chamaillard Rodrigue Dessein | 2011 | World Journal of Gastroenterology2011，17，5： | 5 |
您所在的机构暂未开通此部分的功能，请联系管理员