Potential role of the IL-33/ST2 axis in celiac disease

The IL-33/ST2 axis has been implicated in the pathogenesis of several tissue-specific autoimmune diseases. Celiac disease (CD) is the only autoimmune disease in which both the major genetic factors (HLA-DQ2/DQ8) and etiologic ones (dietary gluten) for susceptibility are known. We have measured serum levels and determined intestinal tissue expression of IL-33 and its receptor soluble ST2 in patients with CD to investigate their association with disease activity. Serum and tissue levels of both IL-33 and sST2 were significantly higher in patients with CD compared with those in control patients without CD. We show that toxic peptides extracted from barley and wheat gliadin significantly stimulate the production of IL-33 and ST2 in cultured peripheral blood mononuclear cell from celiac patients, strongly implicating the IL-33/ST2 axis in the pathogenesis of CD. The higher levels of IL-33 and its receptor ST2 in tissue and serum reflect an active inflammatory state and may represent a potential biomarker for disease activity. A better understanding of IL-33/ST2 release, mode of action, and regulation will be crucial to develop therapeutics that target the IL-33/ST2 pathway to treat CD.Cellular & Molecular Immunology advance online publication, 7 September 2015; doi:10.1038/cmi.2015.85.