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

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‐1...

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Autores principales:	Otgontuya Ganbaatar, Satoru Konnai, Tomohiro Okagawa, Yutaro Nojima, Naoya Maekawa, Yoshiki Ichikawa, Atsushi Kobayashi, Tomoyuki Shibahara, Yojiro Yanagawa, Hidetoshi Higuchi, Yukinari Kato, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	interleukin‐2 PD‐1 PD‐L1 swine diseases Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/c1781704b73940e2bfc77036577955b1
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spelling	oai:doaj.org-article:c1781704b73940e2bfc77036577955b12021-11-12T19:57:15ZProgrammed death‐ligand 1 expression in swine chronic infections and enhancement of interleukin‐2 production via programmed death‐1/programmed death‐ligand 1 blockade2050-452710.1002/iid3.510https://doaj.org/article/c1781704b73940e2bfc77036577955b12021-12-01T00:00:00Zhttps://doi.org/10.1002/iid3.510https://doaj.org/toc/2050-4527Abstract 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‐1 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‐L1 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 antibodies (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‐L1‐expressing cells. The binding of swine PD‐L1 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.Otgontuya GanbaatarSatoru KonnaiTomohiro OkagawaYutaro NojimaNaoya MaekawaYoshiki IchikawaAtsushi KobayashiTomoyuki ShibaharaYojiro YanagawaHidetoshi HiguchiYukinari KatoYasuhiko SuzukiShiro MurataKazuhiko OhashiWileyarticleinterleukin‐2PD‐1PD‐L1swine diseasesImmunologic diseases. AllergyRC581-607ENImmunity, Inflammation and Disease, Vol 9, Iss 4, Pp 1573-1583 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	interleukin‐2 PD‐1 PD‐L1 swine diseases Immunologic diseases. Allergy RC581-607
spellingShingle	interleukin‐2 PD‐1 PD‐L1 swine diseases Immunologic diseases. Allergy RC581-607 Otgontuya Ganbaatar Satoru Konnai Tomohiro Okagawa Yutaro Nojima Naoya Maekawa Yoshiki Ichikawa Atsushi Kobayashi Tomoyuki Shibahara Yojiro Yanagawa Hidetoshi Higuchi Yukinari Kato Yasuhiko Suzuki Shiro Murata Kazuhiko Ohashi Programmed death‐ligand 1 expression in swine chronic infections and enhancement of interleukin‐2 production via programmed death‐1/programmed death‐ligand 1 blockade
description	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‐1 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‐L1 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 antibodies (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‐L1‐expressing cells. The binding of swine PD‐L1 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.
format	article
author	Otgontuya Ganbaatar Satoru Konnai Tomohiro Okagawa Yutaro Nojima Naoya Maekawa Yoshiki Ichikawa Atsushi Kobayashi Tomoyuki Shibahara Yojiro Yanagawa Hidetoshi Higuchi Yukinari Kato Yasuhiko Suzuki Shiro Murata Kazuhiko Ohashi
author_facet	Otgontuya Ganbaatar Satoru Konnai Tomohiro Okagawa Yutaro Nojima Naoya Maekawa Yoshiki Ichikawa Atsushi Kobayashi Tomoyuki Shibahara Yojiro Yanagawa Hidetoshi Higuchi Yukinari Kato Yasuhiko Suzuki Shiro Murata Kazuhiko Ohashi
author_sort	Otgontuya Ganbaatar
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
title_short	Programmed death‐ligand 1 expression in swine chronic infections and enhancement of interleukin‐2 production via programmed death‐1/programmed death‐ligand 1 blockade
title_full	Programmed death‐ligand 1 expression in swine chronic infections and enhancement of interleukin‐2 production via programmed death‐1/programmed death‐ligand 1 blockade
title_fullStr	Programmed death‐ligand 1 expression in swine chronic infections and enhancement of interleukin‐2 production via programmed death‐1/programmed death‐ligand 1 blockade
title_full_unstemmed	Programmed death‐ligand 1 expression in swine chronic infections and enhancement of interleukin‐2 production via programmed death‐1/programmed death‐ligand 1 blockade
title_sort	programmed death‐ligand 1 expression in swine chronic infections and enhancement of interleukin‐2 production via programmed death‐1/programmed death‐ligand 1 blockade
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/c1781704b73940e2bfc77036577955b1
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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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