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Ryusaku Matsuda, Takeshi Kezuka, Chiharu Nishiyama, Yoshihiko Usui, Yoshimichi Matsunaga, Yoko Okunuki, Naoyuki Yamakawa, Hideoki Ogawa, Ko Okumura, Hiroshi Goto; Interleukin-10 Gene-Transfected Mature Dendritic Cells Suppress Murine Experimental Autoimmune Optic Neuritis. Invest. Ophthalmol. Vis. Sci. 2012;53(11):7235-7245. doi: https://doi.org/10.1167/iovs.12-10587.
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© ARVO (1962-2015); The Authors (2016-present)
We have reported that calcitonin gene-related peptide gene-transfected mature dendritic cells (mDC) suppress murine experimental autoimmune optic neuritis (EAON) and experimental autoimmune encephalitis (EAE) via interleukin-10 (IL-10) production. In our study, we examined whether IL-10–transfected mDC prevent development of EAON and EAE.
A plasmid expressing mouse IL-10 was constructed and used to transfect C57BL/6 mouse bone marrow–derived mDC by electroporation methods. C57BL/6 mice (with or without GFP expression) were immunized with myelo-oligodendrocyte glycoprotein35–55 (MOG35–55), and injected intravenously with IL-10–transfected mDC either in the induction or effector phase.
When IL-10–transfected mDC were injected in the induction phase, EAE developed clinically in 60% of mice in the IL-10–transfected group compared to 100% in the mock-transfected group (P < 0.05), and mean pathologic score for EAON was 1.1 in the IL-10–transfected group compared to 2.1 in the mock-transfected group (P < 0.05). When IL-10–transfected mDC were injected in the effector phase, mean EAE clinical scores were not significantly different between the two groups (2.0 vs. 3.0), while the mean EAON pathologic score was lower in the IL-10–transfected group compared to the mock-transfected group (1.0 vs. 2.7, P < 0.05). Delayed hypersensitivity was suppressed significantly in the IL-10–transfected group. Interestingly, the proportions of CD80/86+ and MHC class II+ cells decreased significantly (P < 0.05), whereas Foxp3+ cells increased significantly in the spleen and lymph node in the IL-10–transfected group by flow cytometry analysis. Immunohistochemical analysis demonstrated the localization of IL-10–transfected GFP-expressing mDC not only in the spleen and lymph nodes but also in the inflamed optic nerve.
Treatment with IL-10–expressing mDC was effective in suppressing the development of EAON and EAE.
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