March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Interleukin-10 Gene-transfected Regulatory Dendritic Cells Suppress Murine Experimental Autoimmune Optic Neuritis
Author Affiliations & Notes
  • Ryusaku Matsuda
    Ophthalmology, Tokyo Medical Univ Hospital, Shinjuku-ku, Japan
    Atopy Research Center and Department of Immunology, Juntendo University School of Medicine, Bunnkyou-ku, Japan
  • Takeshi Kezuka
    Ophthalmology, Tokyo Medical Univ Hospital, Shinjuku-ku, Japan
  • Chiharu Nishiyama
    Atopy Research Center and Department of Immunology, Juntendo University School of Medicine, Bunnkyou-ku, Japan
  • Yoshihiko Usui
    Ophthalmology, Tokyo Medical Univ Hospital, Shinjuku-ku, Japan
  • Yoshimichi Matsunaga
    Ophthalmology, Tokyo Medical Univ Hospital, Shinjuku-ku, Japan
  • Yoko Okunuki
    Ophthalmology, Tokyo Medical Univ Hospital, Shinjuku-ku, Japan
  • Naoyuki Yamakawa
    Ophthalmology, Tokyo Medical Univ Hospital, Shinjuku-ku, Japan
  • Hiroshi Goto
    Ophthalmology, Tokyo Medical Univ Hospital, Shinjuku-ku, Japan
  • Footnotes
    Commercial Relationships  Ryusaku Matsuda, None; Takeshi Kezuka, None; Chiharu Nishiyama, None; Yoshihiko Usui, None; Yoshimichi Matsunaga, None; Yoko Okunuki, None; Naoyuki Yamakawa, None; Hiroshi Goto, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 1910. doi:
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    • Get Citation

      Ryusaku Matsuda, Takeshi Kezuka, Chiharu Nishiyama, Yoshihiko Usui, Yoshimichi Matsunaga, Yoko Okunuki, Naoyuki Yamakawa, Hiroshi Goto; Interleukin-10 Gene-transfected Regulatory Dendritic Cells Suppress Murine Experimental Autoimmune Optic Neuritis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1910.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : We have previously reported that calcitonin gene-related peptide-transfected mature dendritic cells (mDCs) suppressed murine experimental autoimmune optic neuritis (EAON) and experimental autoimmune encephalitis (EAE) via IL-10 production. (ARVO, 2009) Here, we investigated whether IL-10 gene-transfected mDCs suppressed EAON and EAE.

Methods: : C57BL6/J mice were immunized with an emulsified mixture of myelin oligodendrocyte glycoprotein (MOG35-55) to establish the EAON-EAE mouse model. A plasmid expressing murine IL-10 was constructed, bone marrow from the C57BL6/J mice (with/without GFP expression) was cultured to generate mDCs, and mDCs were transfected with the mouse IL-10 gene using electroporation. The IL-10 gene-transfected mDCs were injected intravenously immediately following immunization (induction phase). Mice were sacrificed at day 28 after immunization and the spleen, lymph nodes, and optic nerve were resected for immunohistochemical (IHC) evaluation. Using flow cytometry, we analyzed CD80/86 and, MHC class 2 expression in the spleen and lymph node cells.

Results: : In the treatment group which IL-10 gene-transfected mDCs were administered, the numbers of CD80/86-positive and MHC class 2 positive cells were significantly lower in the spleen and lymph nodes as compared to those in the control group (P<0.05). IHC results revealed that GFP-expressing mDCs existed not only in the spleen and lymph nodes but also in the inflamed optic nerve. IL-10 gene-transfected mDCs thus appeared to regulate inflammation via primary and secondary lymph organs and also at the local inflamed site.

Conclusions: : IL-10 gene-transfected mDCs thus effectively suppressed the development of EAON by downregulating the co-stimulatory signal molecules CD80/86 and MHC class 2.

Keywords: optic nerve • gene/expression • gene transfer/gene therapy 
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