Pathogenic effect of interleukin-17A in induction of Sjogren's syndrome-like disease using adenovirus-mediated gene transfer
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 predomina...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | en_US |
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BioMed Central Ltd.
2011
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| Online Access: | http://hdl.handle.net/1721.1/65829 |
| _version_ | 1811075251798278144 |
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| author | Nguyen, Cuong Q. Yin, Hongen Lee, Byung Ha Carcamo, Wendy C. Chiorini, John A. Peck, Ammon B. |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Nguyen, Cuong Q. Yin, Hongen Lee, Byung Ha Carcamo, Wendy C. Chiorini, John A. Peck, Ammon B. |
| author_sort | Nguyen, Cuong Q. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:03:08Z |
| format | Article |
| id | mit-1721.1/65829 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:03:08Z |
| publishDate | 2011 |
| publisher | BioMed Central Ltd. |
| record_format | dspace |
| spelling | mit-1721.1/658292022-09-30T18:35:12Z Pathogenic effect of interleukin-17A in induction of Sjogren's syndrome-like disease using adenovirus-mediated gene transfer Nguyen, Cuong Q. Yin, Hongen Lee, Byung Ha Carcamo, Wendy C. Chiorini, John A. Peck, Ammon B. Massachusetts Institute of Technology. Department of Chemical Engineering Nguyen, Cuong Q. Nguyen, Cuong Q. 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. National Institute of Dental and Craniofacial Research (U.S.) (PHS Grants K99DE018958) National Institute of Allergy and Infectious Diseases (U.S.) (R21AI081952) Sjogren's Syndrome Foundation University of Florida. Center for Orphaned Autoimmune Disorders National Institute of Dental and Craniofacial Research (U.S.) (Intramural research grant) National Institutes of Health (U.S.) 2011-09-14T14:04:24Z 2011-09-14T14:04:24Z 2010-12 2010-11 Article http://purl.org/eprint/type/JournalArticle 1478-6362 1478-6354 http://hdl.handle.net/1721.1/65829 Nguyen, Cuong Q et al. “Pathogenic effect of interleukin-17A in induction of Sjögren’s syndrome-like disease using adenovirus-mediated gene transfer.” Arthritis Research & Therapy 12 (2010): R220. en_US http://dx.doi.org/10.1186/ar3207 Arthritis Research and Therapy Creative Commons Attribution http://creativecommons.org/licenses/by/2.0/ application/pdf BioMed Central Ltd. BMC |
| spellingShingle | Nguyen, Cuong Q. Yin, Hongen Lee, Byung Ha Carcamo, Wendy C. Chiorini, John A. Peck, Ammon B. Pathogenic effect of interleukin-17A in induction of Sjogren's syndrome-like disease using adenovirus-mediated gene transfer |
| title | Pathogenic effect of interleukin-17A in induction of Sjogren's syndrome-like disease using adenovirus-mediated gene transfer |
| title_full | Pathogenic effect of interleukin-17A in induction of Sjogren's syndrome-like disease using adenovirus-mediated gene transfer |
| title_fullStr | Pathogenic effect of interleukin-17A in induction of Sjogren's syndrome-like disease using adenovirus-mediated gene transfer |
| title_full_unstemmed | Pathogenic effect of interleukin-17A in induction of Sjogren's syndrome-like disease using adenovirus-mediated gene transfer |
| title_short | Pathogenic effect of interleukin-17A in induction of Sjogren's syndrome-like disease using adenovirus-mediated gene transfer |
| title_sort | pathogenic effect of interleukin 17a in induction of sjogren s syndrome like disease using adenovirus mediated gene transfer |
| url | http://hdl.handle.net/1721.1/65829 |
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