RT Journal Article
SR Electronic
T1 IL-9 and its receptor are predominantly involved in the pathogenesis of UC
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 743
OP 755
DO 10.1136/gutjnl-2013-305947
VO 64
IS 5
A1 Nalleweg, Nancy
A1 Chiriac, Mircea Teodor
A1 Podstawa, Eva
A1 Lehmann, Christian
A1 Rau, Tilman T
A1 Atreya, Raja
A1 Krauss, Ekaterina
A1 Hundorfean, Gheorghe
A1 Fichtner-Feigl, Stefan
A1 Hartmann, Arndt
A1 Becker, Christoph
A1 Mudter, Jonas
YR 2015
UL http://gut.bmj.com/content/64/5/743.abstract
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.