title: Gene silencing of IL-12 in dendritic cells inhibits autoimmune arthritis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Immunomodulation and Immunotherapy, Nanchang University Medical School, Nanchang, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.forename: Xiufen
authors.initials: X
authors.lastname: Zheng
authors.forename: Igor
authors.initials: I
authors.lastname: Popov
authors.forename: Xusheng
authors.initials: X
authors.lastname: Zhang
authors.forename: Hongmei
authors.initials: H
authors.lastname: Wang
authors.forename: Motohiko
authors.initials: M
authors.lastname: Suzuki
authors.forename: Rosalia De
authors.initials: RD
authors.lastname: Necochea-Campion
authors.forename: Peter W
authors.initials: PW
authors.lastname: French
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.forename: Leo
authors.initials: L
authors.lastname: Siu
authors.forename: David
authors.initials: D
authors.lastname: Koos
authors.forename: Robert D
authors.initials: RD
authors.lastname: Inman
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Min
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D024043:Collagen Type II / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D020868:Gene Silencing; D007156:Immunologic Memory / Q000276:immunology; D056747:Immunomodulation; D018664:Interleukin-12 / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D034741:RNA, Small Interfering / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
chemical_list: D024043:Collagen Type II; D034741:RNA, Small Interfering; D018664:Interleukin-12