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Open Access Highly Accessed Research article

Pathogenic effect of interleukin-17A in induction of Sjögren's syndrome-like disease using adenovirus-mediated gene transfer

Cuong Q Nguyen1234*, Hongen Yin5, Byung Ha Lee3, Wendy C Carcamo3, John A Chiorini5 and Ammon B Peck346

Author Affiliations

1 Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, USA

2 Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave, E25-545, Cambridge MA 02139, USA

3 Department of Oral Biology, University of Florida College of Dentistry, 1600 SW Archer Rd, Gainesville, FL 32610, USA

4 Center for Orphan Autoimmune Disorders, University of Florida College of Dentistry, 1600 SW Archer Rd, Gainesville, FL 32610, USA

5 National Institute of Dental and Craniofacial Research, NIH, 10 Center Drive MSC 1190, Bethesda, MD 20892, USA

6 Department of Pathology, Immunology & Laboratory Medicine, University of Florida College of Medicine, 1600 SW Archer Rd, Gainesville, FL 32610, USA

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Arthritis Research & Therapy 2010, 12:R220  doi:10.1186/ar3207

Published: 23 December 2010

Abstract

Introduction

Sjögren's syndrome (SS) involves a chronic, progressive inflammation primarily of the salivary and lacrimal glands leading to decreased levels of saliva and tears resulting in dry mouth and dry eye diseases. Seminal findings regarding TH17 cell populations that secrete predominantly interleukin (IL)-17A have been shown to play an important role in an increasing number of autoimmune diseases, including SS. In the present study, we investigated the function of IL-17A on the development and onset of SS.

Methods

Adenovirus serotype 5 (Ad5) vectors expressing either IL-17A or LacZ were infused via retrograde cannulation into the salivary glands of C57BL/6J mice between 6 and 8 weeks of age or between 15 and 17 weeks of age. The mice were characterized for SS phenotypes.

Results

Disease profiling indicated that SS-non-susceptible C57BL/6J mice whose salivary glands received the Ad5-IL17A vector developed a SS-like disease profile, including the appearance of lymphocytic foci, increased cytokine levels, changes in antinuclear antibody profiles, and temporal loss of saliva flow.

Conclusions

Induction of SS pathology by IL-17A in SS-non-susceptible mice strongly suggests that IL-17A is an important inflammatory cytokine in salivary gland dysfunction. Thus, localized anti-IL17 therapy may be effective in preventing glandular dysfunction.