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, Kohei Sonoda

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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
Volume62
Issue number3
DOIs
Publication statusPublished - May 1 2018

Fingerprint

Purinergic P2X7 Receptors
Uveitis
T-Lymphocytes
Interleukin-17
Interferons
Th17 Cells
Th1 Cells
Flow Cytometry
Research Design
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this

Crucial role of P2X7 receptor for effector T cell activation in experimental autoimmune uveitis. / Takeda, Atsunobu; Yamada, Hisakata; Hasegawa, Eiichi; Arima, Mitsuru; Notomi, Shoji; Myojin, Sayaka; Yoshimura, Takeru; Hisatomi, Toshio; Enaida, Hiroshi; Yanai, Ryoji; Kimura, Kazuhiro; Ishibashi, Tatsuro; Sonoda, Kohei.

In: Japanese Journal of Ophthalmology, Vol. 62, No. 3, 01.05.2018, p. 398-406.

Research output: Contribution to journalArticle

Takeda, Atsunobu ; Yamada, Hisakata ; Hasegawa, Eiichi ; Arima, Mitsuru ; Notomi, Shoji ; Myojin, Sayaka ; Yoshimura, Takeru ; Hisatomi, Toshio ; Enaida, Hiroshi ; Yanai, Ryoji ; Kimura, Kazuhiro ; Ishibashi, Tatsuro ; Sonoda, Kohei. / Crucial role of P2X7 receptor for effector T cell activation in experimental autoimmune uveitis. In: Japanese Journal of Ophthalmology. 2018 ; Vol. 62, No. 3. pp. 398-406.
@article{37e22abd736245df9e3151e7a993178c,
title = "Crucial role of P2X7 receptor for effector T cell activation in experimental autoimmune uveitis",
abstract = "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.",
author = "Atsunobu Takeda and Hisakata Yamada and Eiichi Hasegawa and Mitsuru Arima and Shoji Notomi and Sayaka Myojin and Takeru Yoshimura and Toshio Hisatomi and Hiroshi Enaida and Ryoji Yanai and Kazuhiro Kimura and Tatsuro Ishibashi and Kohei Sonoda",
year = "2018",
month = "5",
day = "1",
doi = "10.1007/s10384-018-0587-4",
language = "English",
volume = "62",
pages = "398--406",
journal = "Japanese Journal of Ophthalmology",
issn = "0021-5155",
publisher = "Springer Japan",
number = "3",

}

TY - JOUR

T1 - Crucial role of P2X7 receptor for effector T cell activation in experimental autoimmune uveitis

AU - Takeda, Atsunobu

AU - Yamada, Hisakata

AU - Hasegawa, Eiichi

AU - Arima, Mitsuru

AU - Notomi, Shoji

AU - Myojin, Sayaka

AU - Yoshimura, Takeru

AU - Hisatomi, Toshio

AU - Enaida, Hiroshi

AU - Yanai, Ryoji

AU - Kimura, Kazuhiro

AU - Ishibashi, Tatsuro

AU - Sonoda, Kohei

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85044390983&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044390983&partnerID=8YFLogxK

U2 - 10.1007/s10384-018-0587-4

DO - 10.1007/s10384-018-0587-4

M3 - Article

C2 - 29572578

AN - SCOPUS:85044390983

VL - 62

SP - 398

EP - 406

JO - Japanese Journal of Ophthalmology

JF - Japanese Journal of Ophthalmology

SN - 0021-5155

IS - 3

ER -