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Programmed death-ligand 1 expression in swine chronic infections and enhancement of interleukin-2 production via programmed death-1/programmed death-ligand 1 blockade

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Title: Programmed death-ligand 1 expression in swine chronic infections and enhancement of interleukin-2 production via programmed death-1/programmed death-ligand 1 blockade
Authors: Ganbaatar, Otgontuya Browse this author
Konnai, Satoru Browse this author →KAKEN DB
Okagawa, Tomohiro Browse this author →KAKEN DB
Nojima, Yutaro Browse this author
Maekawa, Naoya Browse this author →KAKEN DB
Ichikawa, Yoshiki Browse this author
Kobayashi, Atsushi Browse this author
Shibahara, Tomoyuki Browse this author
Yanagawa, Yojiro Browse this author →KAKEN DB
Higuchi, Hidetoshi Browse this author
Kato, Yukinari Browse this author
Suzuki, Yasuhiko Browse this author →KAKEN DB
Murata, Shiro Browse this author →KAKEN DB
Ohashi, Kazuhiko Browse this author →KAKEN DB
Keywords: interleukin-2
PD-1
PD-L1
swine diseases
Issue Date: 20-Aug-2021
Publisher: John Wiley & Sons
Journal Title: Immunity, inflammation and disease
Publisher DOI: 10.1002/iid3.510
Abstract: Introduction: Chronic infections lead to the functional exhaustion of T cells. Exhausted T cells are phenotypically differentiated by the surface expression of the immunoinhibitory receptor, such as programmed death-1 (PD-1). The inhibitory signal is produced by the interaction between PD-i and its PD-ligand 1 (PD-L1) and impairs the effector functions of T cells. However, the expression dynamics of PD-L1 and the immunological functions of the PD-1/ PD-Ll pathway in chronic diseases of pigs are still poorly understood. In this study, we first analyzed the expression of PD-L1 in various chronic infections in pigs, and then evaluated the immune activation by the blocking assay targeting the swine PD-1/PD-L1 pathway. Methods: In the initial experiments, anti-bovine PD-L1 monoclonal anti-bodies (mAbs) were tested for cross-reactivity with swine PD-L1. Subsequently, immunohistochemical analysis was conducted using the anti-PD-L1 mAb. Finally, we assessed the immune activation of swine peripheral blood mononuclear cells (PBMCs) by the blockade with anti-PD-L1 mAb. Results: Several anti-PD-L1 mAbs tested recognized swine PD-Ll-expressing cells. The binding of swine PD-Ll protein to swine PD-1 was inhibited by some of these cross-reactive mAbs. In addition, immunohistochemical analysis revealed that PD-L1 was expressed at the site of infection in chronic infections of pigs. The PD-L1 blockade increased the production of interleukin-2 from swine PBMCs. Conclusions: These findings suggest that the PD-1/PD-L1 pathway could be also involved in immunosuppression in chronic infections in pigs. This study provides a new perspective on therapeutic strategies for chronic diseases in pigs by targeting immunosuppressive pathways.
Type: article
URI: http://hdl.handle.net/2115/82666
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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