Crucial role of P2X 7 receptor for effector T cell activation in experimental autoimmune uveitis.

Autor: Takeda A; Department of Ophthalmology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan. atakeda@med.kyushu-u.ac.jp.; Clinical Research Center, National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan. atakeda@med.kyushu-u.ac.jp., Yamada H; Division of Host Defense, Research Center for Prevention of Infectious Diseases, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.; Clinical Research Center, National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan., Hasegawa E; Department of Ophthalmology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan., Arima M; Department of Ophthalmology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan., Notomi S; Department of Ophthalmology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan., Myojin S; Department of Ophthalmology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan., Yoshimura T; Department of Ophthalmology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan., Hisatomi T; Department of Ophthalmology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan., Enaida H; Department of Ophthalmology, Faculty of Medicine, Saga University, Saga, Saga, Japan., Yanai R; Department of Ophthalmology, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, Japan., Kimura K; Department of Ophthalmology, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, Japan., Ishibashi T; Department of Ophthalmology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan., Sonoda KH; Department of Ophthalmology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
Jazyk: angličtina
Zdroj: Japanese journal of ophthalmology [Jpn J Ophthalmol] 2018 May; Vol. 62 (3), pp. 398-406. Date of Electronic Publication: 2018 Mar 23.
DOI: 10.1007/s10384-018-0587-4
Abstrakt: 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.
Databáze: MEDLINE
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