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Suppression of Experimental Autoimmune Uveoretinitis by Regulatory Dendritic Cells in Mice
Yoshihiko Usui, MD, PhD;
Masaru Takeuchi, MD, PhD;
Takaaki Hattori, MD, PhD;
Yoko Okunuki, MD, PhD;
Kazumi Nagasawa;
Takeshi Kezuka, MD, PhD;
Ko Okumura, MD, PhD;
Hideo Yagita, PhD;
Hisaya Akiba, PhD;
Hiroshi Goto, MD, PhD
Arch Ophthalmol. 2009;127(4):514-519.
Objective To examine the effects of bone marrow–derived regulatory dendritic cells (DCs) with potent immunoregulatory properties on the development of experimental autoimmune uveoretinitis (EAU).
Methods Bone marrow cells obtained from C57BL/6 mice were treated with granulocyte-macrophage colony-stimulating factor, transforming growth factor β, and interleukin (IL) 10 and stimulated with lipopolysaccharide to produce mature and regulatory DCs. Expression of major histocompatibility complex and costimulatory molecules was analyzed by flow cytometry. Then EAU was induced by immunization with human interphotoreceptor retinoid-binding protein (hIRBP) peptide 1-20, followed by intravenous injection of hIRBP peptide–pulsed regulatory DCs. Control mice received transforming growth factor β and IL-10 nontreated mature DC or phosphate-buffered saline. We evaluated EAU clinically and histopathologically. Immunologic responses to hIRBP peptide were assessed by delayed-type hypersensitivity and T-cell proliferation and cytokine production.
Results Regulatory DCs expressed comparable levels of major histocompatibility complex class II molecules but reduced levels of CD80, CD86, and CD40 compared with mature DCs. Delayed-type hypersensitivity to hIRBP peptide and the development of EAU were markedly suppressed in mice receiving regulatory DCs compared with control mice. Lymph node cells from regulatory DC–treated mice showed significantly reduced hIRBP-specific T-cell proliferation and interferon  production but increased IL-10 production.
Conclusion Administration of regulatory DCs potentially inhibited the development of EAU.
Clinical Relevance Application of regulatory DCs may be a novel candidate for immunotherapy for human endogenous uveitis.
Author Affiliations: Department of Ophthalmology, Tokyo Medical University (Drs Usui, Takeuchi, Hattori, Okunuki, Kezuka, and Goto and Ms Nagasawa), and Department of Immunology, Juntendo University School of Medicine (Drs Okomura, Yagita, and Akiba), Tokyo, Japan.
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