Nalleweg, Nancy and Chiriac, Mircea Teodor and Podstawa, Eva and Lehmann, Christian and Rau, Tilman T. and Atreya, Raja and Krauss, Ekaterina and Hundorfean, Gheorghe and Fichtner-Feigl, Stefan and Hartmann, Arndt and Becker, Christoph and Mudter, Jonas (2015) IL-9 and its receptor are predominantly involved in the pathogenesis of UC. GUT, 64 (5). pp. 743-755. ISSN 0017-5749, 1468-3288
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFLAMMATORY-BOWEL-DISEASE; ULCERATIVE-COLITIS; T-CELLS; HUMAN NEUTROPHILS; EPITHELIAL-CELLS; TH17 CELLS; CYTOKINE; DIFFERENTIATION; EXPRESSION; MICE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Jul 2019 07:26 |
| Last Modified: | 22 Jul 2019 07:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5611 |
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