Overexpression of the IL-33 alarmin in the small intestinal mucosa of celiac disease patients

PÉREZ FEDERICO; HERMOSO MARCELA; DIAZ GIMENEZ DAVID; CHIRDO F.G; RUERA CAROLINA

Valencia

Simposio; 30th Meeting of the European Prolamin Working Group of Prolamin Analysis and Toxicity.; 2016

IL-33, a member of IL-1 family, is mainly expressed by epithelial, endothelial and mesenchymal cells (Moussion, Ortega, & Girard, 2008). In resting cells, it is located principally in the nucleus, where it can regulate the expression of certain genes by its interaction with other transcriptional factors. It has been proved that this protein can be released from the nucleus into the cytoplasm and then to the extracellular medium by different kinds of stimuli inducing strong inflammatory response through its receptor, ST2. The IL-33 receptor is a heterodimeric complex made up of two different proteins ST2L, which actually binds IL-33 and an accessory protein know as IL-1RAc. This receptor is expressed by different cells: lymphocytes, mast cells, NK cells, ILC2, and endothelial, epithelial and mesenchymal cells. The ST2L protein has a splice variant, named as soluble ST2 (sST2) which can be realised into the extracellular space where it works as decoy factor for IL-33 (M. U. Martin, 2013)(N. T. Martin & Martin, 2016). Since the discovery of IL-33 many different functions have been linked to this cytokine. First it was recognised its capacity to promote Th2 responses (Schmitz et al., 2005). More recently, it has been shown that IL-33 may promote Th1 functions. It is clear that IL-33 acts not only as a cytokine, but also as a potent alarm signal, stimulating many pro-inflammatory responses (Haraldsen, Balogh, Pollheimer, Sponheim, & Kochler, 2009). Particularly, necrotic cells, but not apoptotic ones, release an active form of IL-33 with potent biological effects (M. U. Martin, 2013). Based on the functional properties of this molecule, we aimed to investigate whether IL-33 may play a role in Celiac Disease (CD) pathogenesis. It has been recently observed that CD patients present increased levels of IL-33 (López-Casado, Lorite, Palomeque, & Torres, 2015). In the present work, we evaluate the expression of IL-33 and its receptor in human intestinal mucosa. These are the initial studies in order to link the biology of IL-33 and the mechanisms of CD pathogenesis.