title: Central role of IL-17/Th17 immune responses and the gut microbiota in the pathogenesis of intestinal fibrosis.
abstract: OBJECTIVE
  Intestinal fibrosis is a serious, yet common, outcome in patients with inflammatory bowel disease (IBD). Despite advances in developing novel treatment modalities to control chronic gut inflammation characteristic of IBD, no effective antifibrotic therapies exist to date. As such, a deeper understanding of the molecular mechanisms underlying intestinal fibrosis and the availability of relevant animal models are critical to move this area of investigation forward.
  
  
  RESULTS
  Emerging concepts in the pathogenesis of intestinal fibrosis include the central role of interleukin (IL)-17 and Th17 immune responses, although their precise contribution to chronic inflammation and IBD remains controversial. Other novel mediators of intestinal fibrosis, such as tumor necrosis factor-like ligand 1A and components of the renin-angiotensin system, support the importance of IL-17. Additionally, recent studies utilizing novel mouse models highlight the significance of the gut microbiota and link components of bacterial sensing, including nucleotide-binding oligomerization domain-containing protein 2, to IL-17/Th17 immune responses in the development of inflammation-associated intestinal fibrosis.
  
  
  CONCLUSIONS
  Recent progress in identifying key mediators, novel animal models, and important mechanistic pathways in the pathogenesis of intestinal fibrosis holds promise for the development of effective antifibrotics in an area of significant, unmet clinical need.
authors.affiliation: aDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA bDepartment of Gastroenterology, Guy's and St. Thomas' Hospitals/University College London, London, United Kingdom.
authors.forename: Shuvra
authors.initials: S
authors.lastname: Ray
authors.forename: Carlo
authors.initials: C
authors.lastname: De Salvo
authors.forename: Theresa T
authors.initials: TT
authors.lastname: Pizarro
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D004926:Escherichia coli / Q000276:immunology; D004927:Escherichia coli Infections / Q000150:complications / Q000276:immunology / Q000503:physiopathology; D005355:Fibrosis / Q000209:etiology / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D020381:Interleukin-17 / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology*; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D064307:Microbiota / Q000276:immunology*; D009687:Nuclear Proteins / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000276:immunology
chemical_list: D020381:Interleukin-17; D008565:Membrane Proteins; D009687:Nuclear Proteins; C575109:Samp1 protein, mouse; C117026:TNFSF15 protein, human; C505947:Tnfsf15 protein, mouse; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15