title: Cutting edge: IL-1 controls the IL-23 response induced by gliadin, the etiologic agent in celiac disease.
abstract: IL-23 has been implicated in the pathogenesis of several tissue-specific autoimmune diseases. Currently, celiac disease (CD) is the only autoimmune disease in which both the major genetic (95% HLA-DQ2(+)) and etiologic factors (dietary glutens) for susceptibility are known. We demonstrate that wheat gliadin induces significantly greater production of IL-23, IL-1beta, and TNF-alpha in PBMC from CD patients compared with HLA-DQ2(+) healthy controls, strongly advocating a role for IL-23 in the pathogenesis of CD. Moreover, IL-1beta alone triggered IL-23 secretion and the IL-1R antagonist inhibited this response in PBMC and purified monocytes. This sequence of events was replicated by beta-glucan, another substance known to induce IL-23 production. Our results suggest that gliadin and beta-glucan stimulate IL-23 secretion through induction of the IL-1 signaling pathway and reveal for the first time that the IL-1 system regulates IL-23 production. These findings may provide therapeutic targets for this disease and other inflammatory conditions mediated by IL-23.
authors.affiliation: Pathology Department, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Harris
authors.forename: Alessio
authors.initials: A
authors.lastname: Fasano
authors.forename: Dean L
authors.initials: DL
authors.lastname: Mann
mesh_terms: D002446:Celiac Disease / Q000276:immunology*; D002478:Cells, Cultured; D005903:Gliadin / Q000009:adverse effects*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D053583:Interleukin-1beta / Q000096:biosynthesis; D053759:Interleukin-23 / Q000096:biosynthesis* / Q000378:metabolism* / Q000502:physiology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000502:physiology; D014176:Protein Biosynthesis / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D007375:Interleukin-1; D053583:Interleukin-1beta; D053759:Interleukin-23; D010446:Peptide Fragments; D005903:Gliadin