Immunoregulatory role of ocular macrophages: The macrophages produce RANTES to suppress experimental autoimmune uveitis

Koh Hei Sonoda, Yukio Sasa, Hong Qiao, Chikako Tsutsumi, Toshio Hisatomi, Sohtaro Komiyama, Toshiaki Kubota, Taiji Sakamoto, Yoh Ichi Kawano, Tatsuro Ishibashi

研究成果: ジャーナルへの寄稿学術誌査読

47 被引用数 (Scopus)

抄録

Murine experimental autoimmune uveitis (EAU) is a model of human uveitis. Ocular-infiltrating macrophages play a crucial role in the generation of tissue damage in EAU. In fact, several chemokines are actually produced in the inflamed eye. The aim of this study was to elucidate the role of ocular macrophage-derived chemokines in EAU. C57BL/6 mice were immunized with human interphotoreceptor retinoid binding protein peptide 1-20, and the EAU severity was scored at multiple time points based on microscopic fundus observations (retinal vascular dilatation and exudates) and histological examinations. The peak inflammatory response was observed 1 wk (day 16) after the beginning of macrophage infiltration to the eye (day 9). Ocular-infiltrating cells were enriched or depleted of macrophages by magnetic beads and analyzed by real-time RT-PCR for chemokine mRNA production. We found that only the macrophage-enriched cells from the eye produced RANTES, and thus proposed that macrophage-derived RANTES facilitated the ocular inflammations. In contrast to our postulate, neutralization of RANTES by specific Ab in vivo on days 9 and 13 exacerbated EAU. We also found that the ratio of ocular CD4/CD8 T cells was markedly increased after treatment. As a result, RANTES neutralization might exacerbate EAU by modulating the type of T cell subsets recruited to the eye. In conclusion, our data provide insight into the immunoregulatory role of macrophages and RANTES in the pathogenesis of ocular inflammation. Not all macrophage-derived chemokines cause local inflammation, since RANTES produced by ocular macrophages appears to suppress EAU.

本文言語英語
ページ(範囲)2652-2659
ページ数8
ジャーナルJournal of Immunology
171
5
DOI
出版ステータス出版済み - 9月 1 2003

!!!All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 免疫学

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