Gene silencing of IL-12 in dendritic cells inhibits autoimmune arthritis
<p>Abstract</p> <p>Background</p> <p>We have previously demonstrated that immune modulation can be accomplished by administration of gene silenced dendritic cells (DC) using siRNA. In this study, we demonstrate the therapeutic utilization of shRNA-modified DC as an anti...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-01-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://www.translational-medicine.com/content/10/1/19 |
| _version_ | 1818786943353225216 |
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| author | Li Rong Zheng Xiufen Popov Igor Zhang Xusheng Wang Hongmei Suzuki Motohiko De Necochea-Campion Rosalia French Peter W Chen Di Siu Leo Koos David Inman Robert D Min Wei-Ping |
| author_facet | Li Rong Zheng Xiufen Popov Igor Zhang Xusheng Wang Hongmei Suzuki Motohiko De Necochea-Campion Rosalia French Peter W Chen Di Siu Leo Koos David Inman Robert D Min Wei-Ping |
| author_sort | Li Rong |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>We have previously demonstrated that immune modulation can be accomplished by administration of gene silenced dendritic cells (DC) using siRNA. In this study, we demonstrate the therapeutic utilization of shRNA-modified DC as an antigen-specific tolerogenic vaccine strategy for autoimmune arthritis.</p> <p>Methods</p> <p>A shRNA that specifically targets IL-12 p35 was designed and cloned into a plasmid vectors (IL-12 shRNA). Bone marrow-derived DC from DBA/1 mice were transfected with the IL-12 shRNA construct in vitro. Mice with collagen II (CII)-induced arthritis (CIA) were treated with the modified DCs expressing the shRNA. Recall response and disease progression were assessed.</p> <p>Results</p> <p>After gene silencing of IL-12 in DC, DC were shown to selectively inhibit T cell proliferation on recall responses and in an MLR. In murine CIA, we demonstrated that administration of IL-12 shRNA-expressing DC that were pulsed with CII inhibited progression of arthritis. The therapeutic effects were evidenced by decreased clinical scores, inhibition of inflammatory cell infiltration in the joint, and suppression of T cell and B cell responses to CII.</p> <p>Conclusion</p> <p>We demonstrate a novel tolerance-inducing protocol for the treatment of autoimmune inflammatory joint disease in which the target antigen is known, utilizing DNA-directed RNA interference.</p> |
| first_indexed | 2024-12-18T13:59:54Z |
| format | Article |
| id | doaj.art-b0657d987d9d4a9db5b14b6cd4948c31 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-18T13:59:54Z |
| publishDate | 2012-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-b0657d987d9d4a9db5b14b6cd4948c312022-12-21T21:05:21ZengBMCJournal of Translational Medicine1479-58762012-01-011011910.1186/1479-5876-10-19Gene silencing of IL-12 in dendritic cells inhibits autoimmune arthritisLi RongZheng XiufenPopov IgorZhang XushengWang HongmeiSuzuki MotohikoDe Necochea-Campion RosaliaFrench Peter WChen DiSiu LeoKoos DavidInman Robert DMin Wei-Ping<p>Abstract</p> <p>Background</p> <p>We have previously demonstrated that immune modulation can be accomplished by administration of gene silenced dendritic cells (DC) using siRNA. In this study, we demonstrate the therapeutic utilization of shRNA-modified DC as an antigen-specific tolerogenic vaccine strategy for autoimmune arthritis.</p> <p>Methods</p> <p>A shRNA that specifically targets IL-12 p35 was designed and cloned into a plasmid vectors (IL-12 shRNA). Bone marrow-derived DC from DBA/1 mice were transfected with the IL-12 shRNA construct in vitro. Mice with collagen II (CII)-induced arthritis (CIA) were treated with the modified DCs expressing the shRNA. Recall response and disease progression were assessed.</p> <p>Results</p> <p>After gene silencing of IL-12 in DC, DC were shown to selectively inhibit T cell proliferation on recall responses and in an MLR. In murine CIA, we demonstrated that administration of IL-12 shRNA-expressing DC that were pulsed with CII inhibited progression of arthritis. The therapeutic effects were evidenced by decreased clinical scores, inhibition of inflammatory cell infiltration in the joint, and suppression of T cell and B cell responses to CII.</p> <p>Conclusion</p> <p>We demonstrate a novel tolerance-inducing protocol for the treatment of autoimmune inflammatory joint disease in which the target antigen is known, utilizing DNA-directed RNA interference.</p>http://www.translational-medicine.com/content/10/1/19shRNAIL-12Dendritic cellsAutoimmunityCollagen-induced arthritis |
| spellingShingle | Li Rong Zheng Xiufen Popov Igor Zhang Xusheng Wang Hongmei Suzuki Motohiko De Necochea-Campion Rosalia French Peter W Chen Di Siu Leo Koos David Inman Robert D Min Wei-Ping Gene silencing of IL-12 in dendritic cells inhibits autoimmune arthritis Journal of Translational Medicine shRNA IL-12 Dendritic cells Autoimmunity Collagen-induced arthritis |
| title | Gene silencing of IL-12 in dendritic cells inhibits autoimmune arthritis |
| title_full | Gene silencing of IL-12 in dendritic cells inhibits autoimmune arthritis |
| title_fullStr | Gene silencing of IL-12 in dendritic cells inhibits autoimmune arthritis |
| title_full_unstemmed | Gene silencing of IL-12 in dendritic cells inhibits autoimmune arthritis |
| title_short | Gene silencing of IL-12 in dendritic cells inhibits autoimmune arthritis |
| title_sort | gene silencing of il 12 in dendritic cells inhibits autoimmune arthritis |
| topic | shRNA IL-12 Dendritic cells Autoimmunity Collagen-induced arthritis |
| url | http://www.translational-medicine.com/content/10/1/19 |
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