Document information

1 vote

IL-1 regulates the IL-23 response to wheat gliadin, the etiologic agent of Celiac Disease

Kristina M. Harris¹, Alessio Fasano², & Dean L. Mann¹

Correspondence: (Login to view email address)

1. University of Maryland School of Medicine, Pathology
2. University of Maryland School of Medicine, Mucosal Biology Research Center

PDF (24.3 KB)

Document Type:

Manuscript

Date:

Received 13 May 2008 16:55 UTC; Posted 13 May 2008

Subjects:

Genetics, Immunology

Tags:

• innate immunity
• autoimmunity
• IL-1
• IL-23
• Celiac Disease

Abstract:

Celiac disease (CD) is an autoimmune disease prevalent in ~1% of the general population. CD is unique because both the major genetic (Human Leukocyte Antigen-DQ2/DQ8 alleles) and etiologic factors (dietary glutens) for susceptibility are known. While these alleles are responsible for the inappropriate T cell response that characterizes CD, they are not sufficient since most HLA-DQ2+/DQ8+ individuals exposed to glutens never develop disease. The reasons for this have not been explained; however our novel findings strongly advocate a role for interleukin-23 (IL-23) in the immunopathogenesis of CD. We demonstrate that wheat gliadin stimulates monocytes to produce significantly higher amounts of inflammatory cytokines IL-1b, IL-23, and tumor necrosis factor-a (TNFa) in CD patients compared to HLA-DQ2+ healthy individuals. Furthermore, we determine that IL-1 signalling is obligatory for production of IL-23, since IL-1b triggers IL-23 secretion in a dose-dependent manner and IL-1 receptor antagonist (IL-1ra) blocks IL-23 responses to gliadin. Our results suggest that gliadin activation of monocytes and the subsequent robust secretion of IL-1b and IL-23 initiate the immune response cascade that is manifest as CD, and reveal for the first time that the IL-1 system regulates production of IL-23. The discovery of IL-23 has highlighted the critical role of the innate immune response in autoimmunity and other inflammatory conditions. We anticipate that our novel findings will lead to the discovery of therapeutic targets for this disease and other inflammatory diseases mediated by IL-23.

Discussion

Votes:

1 vote

(Login to vote)

Comments:

0 comments

(Login to post a comment)

Share:

(Login to share with a colleague)

Additional information

License:

This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Harris, Kristina, Fasano, Alessio, and Mann, Dean. IL-1 regulates the IL-23 response to wheat gliadin, the etiologic agent of Celiac Disease. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2008.1882.1> (2008)

Version info:

Other versions of this document in Nature Precedings

None.

Other versions of this document elsewhere on the web

None known.

Submit a new version link