Crucial role of P2X7 receptor for effector T cell activation in experimental autoimmune uveitis

Atsunobu Takeda, Hisakata Yamada, Eiichi Hasegawa, Mitsuru Arima, Shoji Notomi, Sayaka Myojin, Takeru Yoshimura, Toshio Hisatomi, Hiroshi Enaida, Ryoji Yanai, Kazuhiro Kimura, Tatsuro Ishibashi, Koh Hei Sonoda

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Purpose: To investigate the roles of P2X7 receptors (P2RX7) in the pathogenesis of experimental autoimmune uveoretinitis (EAU). Study design: Experimental. Methods: Either wild-type (P2rx7+/+) or P2rx7-deficient (P2rx7) mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) peptide 1-20. Severity of EAU was evaluated clinically and histopathologically. The induction of IRBP-specific proliferation and cytokines in draining lymph nodes was assessed by enzyme-linked immunosorbent assays (ELISA). The frequency of activation markers was examined by flow cytometry. Furthermore, inhibitory roles of systemic administration of Brilliant Blue G (BBG), an antagonist for P2RX7, in EAU were also assessed in the wild-type mice. Results: The severity of EAU in P2rx7 mice was reduced as compared with that in P2rx7+/+ mice, both clinically and histopathologically. IRBP-specific proliferation in P2rx7 on day 16 was slightly decreased compared to that in P2rx7+/+ mice. The induction of IRBP-specific interferon (IFN)-γ and interleukin (IL)-17 in P2rx7 mice on day 16 was lower than that in P2rx7+/+ mice. The up-regulation of surface expression of activation markers such as CD25, CD44, and CD69 in response to TCR stimulation in P2rx7 mice was decreased as compared with that in P2rx7+/+ mice. Furthermore, neutralization of P2RX7 in vivo by BBG suppressed EAU clinically and histopathologically. IRBP-specific IFN-γ and IL-17 induction in BBG-treated mice was significantly lower than that in vehicle-treated mice. Conclusion: The results suggest that P2RX7 is a novel preventative therapeutic target for uveitis as it suppresses the effector functions of both Th1 and Th17 cell responses.

Original languageEnglish
Pages (from-to)398-406
Number of pages9
JournalJapanese Journal of Ophthalmology
Issue number3
Publication statusPublished - May 1 2018

All Science Journal Classification (ASJC) codes

  • Ophthalmology


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