PT  - JOURNAL ARTICLE
AU  - Nalleweg, Nancy
AU  - Chiriac, Mircea Teodor
AU  - Podstawa, Eva
AU  - Lehmann, Christian
AU  - Rau, Tilman T
AU  - Atreya, Raja
AU  - Krauss, Ekaterina
AU  - Hundorfean, Gheorghe
AU  - Fichtner-Feigl, Stefan
AU  - Hartmann, Arndt
AU  - Becker, Christoph
AU  - Mudter, Jonas
TI  - IL-9 and its receptor are predominantly involved in the pathogenesis of UC
AID  - 10.1136/gutjnl-2013-305947
DP  - 2015 May 01
TA  - Gut
PG  - 743--755
VI  - 64
IP  - 5
4099  - http://gut.bmj.com/content/64/5/743.short
4100  - http://gut.bmj.com/content/64/5/743.full
SO  - Gut2015 May 01; 64
AB  - 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.