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Cutting Edge: IL-1 Controls the IL-23 Response Induced by Gliadin, the Etiologic Agent in Celiac Disease¹

Kristina M. Harris^*, Alessio Fasano and Dean L. Mann^2,*

^* Pathology Department and Mucosal Biology Research Center, University of Maryland School of Medicine, Baltimore, MD 21201

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-1β, and TNF- 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-1β 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 β-glucan, another substance known to induce IL-23 production. Our results suggest that gliadin and β-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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Funding for this project was provided by an Internal Research Grant from Department of Pathology, University of Maryland School of Medicine, Baltimore, MD. These studies were partially supported by National Institutes of Health Grant DK078699 to A.F.

² Address correspondence and reprint requests to Dr. Dean L. Mann,10 South Pine Street, Medical School Teaching Facility Building, Room 8-56, Baltimore, MD 21201. E-mail address: dmann001{at}umaryland.edu

³ Abbreviations used in this paper: CD, celiac disease; IL-1ra, IL-1R antagonist; immDC, immature monocyte-derived dendritic cell; PTG, pepsin-trypsin digest of gliadin.

⁴ The online version of this article contains supplemental material.