IL-9 and its receptor are predominantly involved in the pathogenesis of UC

Language
en
Document Type
Article
Issue Date
2017-01-26
Issue Year
2015
Authors
Nalleweg, Nancy
Chiriac, Mircea Teodor
Podstawa, Eva
Lehmann, Christian
Rau, Tilman T.
Atreya, Raja
Krauss, Ekaterina
Hundorfean, Gheorghe
Fichtner-Feigl, Stefan
Hartmann, Arndt
Editor
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.

Journal Title
Gut
Volume
64
Issue
5
Citation
Gut 64.5 (2015): S. 743-755. <http://gut.bmj.com/content/64/5/743>
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