Development of an intravital imaging system for the synovial tissue reveals the dynamics of CTLA-4 Ig in vivo

Abstract There have been many attempts to visualize the inflamed joints using multiphoton microscopy. However, due to the hypervascular and multilayered structure of the inflamed synovium, intravital imaging of the deep synovial tissue has been difficult. Here, we established original intravital ima...

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Autores principales:	Tetsuo Hasegawa, Junichi Kikuta, Takao Sudo, Erika Yamashita, Shigeto Seno, Tsutomu Takeuchi, Masaru Ishii
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ffceba66e2cb41f995119f789c09911f
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spelling	oai:doaj.org-article:ffceba66e2cb41f995119f789c09911f2021-12-02T16:43:38ZDevelopment of an intravital imaging system for the synovial tissue reveals the dynamics of CTLA-4 Ig in vivo10.1038/s41598-020-70488-y2045-2322https://doaj.org/article/ffceba66e2cb41f995119f789c09911f2020-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-70488-yhttps://doaj.org/toc/2045-2322Abstract There have been many attempts to visualize the inflamed joints using multiphoton microscopy. However, due to the hypervascular and multilayered structure of the inflamed synovium, intravital imaging of the deep synovial tissue has been difficult. Here, we established original intravital imaging systems to visualize synovial tissue and pathological osteoclasts at the pannus–bone interface using multiphoton microscopy. Combined with fluorescence-labeling of CTLA-4 Ig, a biological agent used for the treatment of rheumatoid arthritis, we identified that CTLA-4 Ig was distributed predominantly within the inflamed synovium and bound to CX3CR1+ macrophages and CD140a+ fibroblasts 6 h after injection, but not to mature osteoclasts. Intravital imaging of blood and lymphatic vessels in the inflamed synovium further showed that extravasated CTLA-4 Ig was immediately drained through lymphatic vessels under acute arthritic conditions, but the drainage activity was retarded under chronic conditions. These results indicate that this intravital synovial imaging system can serve as a platform for exploring the dynamics of immune cells, osteoclasts, and biological agents within the synovial microenvironment in vivo.Tetsuo HasegawaJunichi KikutaTakao SudoErika YamashitaShigeto SenoTsutomu TakeuchiMasaru IshiiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tetsuo Hasegawa Junichi Kikuta Takao Sudo Erika Yamashita Shigeto Seno Tsutomu Takeuchi Masaru Ishii Development of an intravital imaging system for the synovial tissue reveals the dynamics of CTLA-4 Ig in vivo
description	Abstract There have been many attempts to visualize the inflamed joints using multiphoton microscopy. However, due to the hypervascular and multilayered structure of the inflamed synovium, intravital imaging of the deep synovial tissue has been difficult. Here, we established original intravital imaging systems to visualize synovial tissue and pathological osteoclasts at the pannus–bone interface using multiphoton microscopy. Combined with fluorescence-labeling of CTLA-4 Ig, a biological agent used for the treatment of rheumatoid arthritis, we identified that CTLA-4 Ig was distributed predominantly within the inflamed synovium and bound to CX3CR1+ macrophages and CD140a+ fibroblasts 6 h after injection, but not to mature osteoclasts. Intravital imaging of blood and lymphatic vessels in the inflamed synovium further showed that extravasated CTLA-4 Ig was immediately drained through lymphatic vessels under acute arthritic conditions, but the drainage activity was retarded under chronic conditions. These results indicate that this intravital synovial imaging system can serve as a platform for exploring the dynamics of immune cells, osteoclasts, and biological agents within the synovial microenvironment in vivo.
format	article
author	Tetsuo Hasegawa Junichi Kikuta Takao Sudo Erika Yamashita Shigeto Seno Tsutomu Takeuchi Masaru Ishii
author_facet	Tetsuo Hasegawa Junichi Kikuta Takao Sudo Erika Yamashita Shigeto Seno Tsutomu Takeuchi Masaru Ishii
author_sort	Tetsuo Hasegawa
title	Development of an intravital imaging system for the synovial tissue reveals the dynamics of CTLA-4 Ig in vivo
title_short	Development of an intravital imaging system for the synovial tissue reveals the dynamics of CTLA-4 Ig in vivo
title_full	Development of an intravital imaging system for the synovial tissue reveals the dynamics of CTLA-4 Ig in vivo
title_fullStr	Development of an intravital imaging system for the synovial tissue reveals the dynamics of CTLA-4 Ig in vivo
title_full_unstemmed	Development of an intravital imaging system for the synovial tissue reveals the dynamics of CTLA-4 Ig in vivo
title_sort	development of an intravital imaging system for the synovial tissue reveals the dynamics of ctla-4 ig in vivo
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/ffceba66e2cb41f995119f789c09911f
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Development of an intravital imaging system for the synovial tissue reveals the dynamics of CTLA-4 Ig in vivo

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