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Original article
IL-9 and its receptor are predominantly involved in the pathogenesis of UC
  1. Nancy Nalleweg1,
  2. Mircea Teodor Chiriac1,2,3,
  3. Eva Podstawa1,
  4. Christian Lehmann4,
  5. Tilman T Rau5,
  6. Raja Atreya1,
  7. Ekaterina Krauss1,
  8. Gheorghe Hundorfean1,
  9. Stefan Fichtner-Feigl6,
  10. Arndt Hartmann5,
  11. Christoph Becker1,
  12. Jonas Mudter1,7
  1. 1Department of Medicine 1, University of Erlangen-Nuremberg, Erlangen, Germany
  2. 2Molecular Biology Center, Interdisciplinary Research Institute on Bio-Nano-Sciences, Cluj-Napoca, Romania
  3. 3Department of Biology, Babes-Bolyai University, Cluj-Napoca, Romania
  4. 4Department of Dermatology, Laboratory of Dendritic Cell Biology, University of Erlangen-Nuremberg, Erlangen, Germany
  5. 5Institute of Pathology, University of Erlangen-Nuremberg, Erlangen, Germany
  6. 6Department of Surgery, University of Regensburg, Regensburg, Germany
  7. 7Department of Gastroenterology, Sana Clinic, Ostholstein, Germany
  1. Correspondence to Dr Jonas Mudter, Sana Clinic Ostholstein, Hospitalstraße 22, Eutin 23701, Germany; jonas.mudter{at}sana.de

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.

Design 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.

  • IBD
  • Ulcerative Colitis
  • Interleukins
  • Leukocytes

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