Review Experimental colitis models: Insights into the pathogenesis of inflammatory bowel disease and translational issues Vassilis Valatas a,n , Giorgos Bamias b , George Kolios c a Laboratory of Gastroenterology, Faculty of Medicine, University of Crete, Greece b Academic Department of Gastroenterology, Laikon Hospital, Kapodistriakon University of Athens, Athens, Greece c Laboratory of Pharmacology, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece article info Article history: Received 19 October 2014 Received in revised form 3 February 2015 Accepted 12 March 2015 Available online 23 March 2015 Keywords: Inflammatory bowel disease Crohn's disease Ulcerative colitis Experimental colitis Animal models Translation abstract Inflammatory bowel diseases, ulcerative colitis and Crohn's disease are characterized by chronic relapsing inflammation of the gastrointestinal tract of unknown etiology that seems to be the consequence of a genetically driven dysregulated immune response against various local and environ- mental triggers through a defective epithelial barrier. During the last decades, a large number of animal experimental models of intestinal inflammation have been generated and provided valuable insights into the mechanisms that either maintain mucosal homeostasis or drive intestinal inflammation. Their study enabled the identification of various treatment targets and the development a large pipeline of new drugs, mostly biologics. Safety and therapeutic efficacy of these agents have been evaluated in a large number of clinical trials but only a minority has reached the clinic so far. Translational successes but mostly translational failures have prompted to re-evaluate results of efficacy and safety generated by pre-clinical testing and to re-examine the way to interpret experimental in vivo data. This review examines the contribution of the most popular experimental colitis models to our understanding of the pathogenesis of human inflammatory bowel diseases and their translational input in drug development and discusses ways to improve translational outcome. & 2015 Elsevier B.V. All rights reserved. Contents 1. Introduction ........................................................................................................ 253 2. Experimental colitis models with epithelial barrier defects .................................................................. 254 3. Experimental colitis models with innate immunity defects .................................................................. 256 3.1. Mice with NOD and autophagy defects ............................................................................ 256 4. Experimental models of colitis characterized by aberrant adaptive T-cell responses............................................... 257 4.1. Excessive effector cell responses .................................................................................. 257 4.2. Regulatory and effector T cell imbalance ........................................................................... 258 4.3. Findings in Human IBD and translational outcomes .................................................................. 259 5. Strategies to increase the translational value of experimental colitis models .................................................... 260 References ............................................................................................................. 261 1. Introduction Inflammatory bowel disease (IBD) comprises of two separate clinical entities ulcerative colitis (UC) and Crohn's disease (CD). Both are characterized by chronic relapsing inflammation of the gastrointestinal tract of unknown etiology. The principal hypoth- esis for their pathogenesis is that intestinal inflammation repre- sents the end result of a genetically driven dysregulated immune response against antigens of the intestinal microflora though a Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/ejphar European Journal of Pharmacology http://dx.doi.org/10.1016/j.ejphar.2015.03.017 0014-2999/& 2015 Elsevier B.V. All rights reserved. n Correspondence to: Department of Gastroenterology, University Hospital of Heraklion, PO Box 1352, Voutes, Heraklion GR-71100, Crete, Greece. Tel.: þ30 2810392356; fax: þ30 2810542085. E-mail addresses: valatas@gmail.com (V. Valatas), gbamias@gmail.com (G. Bamias), gkolios@med.duth.gr (G. Kolios). European Journal of Pharmacology 759 (2015) 253–264