title: IL-9 and its receptor are predominantly involved in the pathogenesis of UC.
abstract: OBJECTIVE
  Several pathogenic roles attributed over the past two decades to either T helper (Th)1 or Th2 cells are increasingly becoming associated with interleukin (IL)-17 and most recently IL-9 signalling. However, the implication of IL-9 in IBD has not been addressed so far.
  
  
  METHODS
  We investigated the expression of IL-9 and IL-9R by using peripheral blood, biopsies and surgical samples. We addressed the functional role of IL-9 signalling by analysis of downstream effector proteins. Using Caco-2 cell monolayers we followed the effect of IL-9 on wound healing.
  
  
  RESULTS
  IL-9 mRNA expression was significantly increased in inflamed samples from patients with UC as compared with controls. CD3(+) T cells were major IL-9-expressing cells and some polymorphonuclear leucocytes (PMN) also expressed IL-9. IL-9 was co-localised with the key Th9 transcription factors interferon regulatory factor 4 and PU.1. Systemically, IL-9 was abundantly produced by activated peripheral blood lymphocytes, whereas its receptor was overexpressed on gut resident and circulating PMN. IL-9 stimulation of the latter induced IL-8 production in a dose-dependent manner and rendered PMN resistant to apoptosis suggesting a functional role for IL-9R signalling in the propagation of gut inflammation. Furthermore, IL-9R was overexpressed on gut epithelial cells and IL-9 induced STAT5 activation in these cells. Moreover, IL-9 inhibited the growth of Caco-2 epithelial cell monolayers in wound healing experiments.
  
  
  CONCLUSIONS
  Our results provide evidence that IL-9 is predominantly involved in the pathogenesis of UC suggesting that targeting IL-9 might become a therapeutic option for patients with UC.
authors: Department of Medicine 1, University of Erlangen-Nuremberg, Erlangen, Germany.
authors: Nancy
authors: N
authors: Nalleweg
authors: Department of Medicine 1, University of Erlangen-Nuremberg, Erlangen, Germany Molecular Biology Center, Interdisciplinary Research Institute on Bio-Nano-Sciences, Cluj-Napoca, Romania Department of Biology, Babes-Bolyai University, Cluj-Napoca, Romania.
authors: Mircea Teodor
authors: MT
authors: Chiriac
authors: Department of Medicine 1, University of Erlangen-Nuremberg, Erlangen, Germany.
authors: Eva
authors: E
authors: Podstawa
authors: Department of Dermatology, Laboratory of Dendritic Cell Biology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors: Christian
authors: C
authors: Lehmann
authors: Institute of Pathology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors: Tilman T
authors: TT
authors: Rau
authors: Department of Medicine 1, University of Erlangen-Nuremberg, Erlangen, Germany.
authors: Raja
authors: R
authors: Atreya
authors: Department of Medicine 1, University of Erlangen-Nuremberg, Erlangen, Germany.
authors: Ekaterina
authors: E
authors: Krauss
authors: Department of Medicine 1, University of Erlangen-Nuremberg, Erlangen, Germany.
authors: Gheorghe
authors: G
authors: Hundorfean
authors: Department of Surgery, University of Regensburg, Regensburg, Germany.
authors: Stefan
authors: S
authors: Fichtner-Feigl
authors: Institute of Pathology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors: Arndt
authors: A
authors: Hartmann
authors: Department of Medicine 1, University of Erlangen-Nuremberg, Erlangen, Germany.
authors: Christoph
authors: C
authors: Becker
authors: Department of Medicine 1, University of Erlangen-Nuremberg, Erlangen, Germany Department of Gastroenterology, Sana Clinic, Ostholstein, Germany.
authors: Jonas
authors: J
authors: Mudter
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000276:immunology; D017252:CD3 Complex / Q000378:metabolism; D018938:Caco-2 Cells; D003093:Colitis, Ulcerative / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D039441:Integrin alpha4 / Q000097:blood; D039641:Integrin beta Chains / Q000097:blood; D050835:Interferon Regulatory Factors / Q000096:biosynthesis; D016906:Interleukin-9 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D053651:Receptors, Interleukin-9 / Q000037:antagonists & inhibitors / Q000276:immunology*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D015534:Trans-Activators / Q000096:biosynthesis; D015854:Up-Regulation / Q000276:immunology; D014945:Wound Healing / Q000276:immunology; D055815:Young Adult; D000099232:Proto-Oncogene Protein Spi-1; D000099218:Interferon Regulatory Factor-4
chemical_list: D017252:CD3 Complex; D039441:Integrin alpha4; D039641:Integrin beta Chains; D050835:Interferon Regulatory Factors; D016906:Interleukin-9; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D053651:Receptors, Interleukin-9; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; D000099218:Interferon Regulatory Factor-4; C091368:integrin beta7
keywords: IBD; Interleukins; Leukocytes; Ulcerative Colitis