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

Hasegawa, Tetsuo; Kikuta, Junichi; Sudo, Takao; Yamashita, Erika; Seno, Shigeto; Takeuchi, Tsutomu; Ishii, Masaru

doi:https://doi.org/10.1038/s41598-020-70488-y

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

Hasegawa, Tetsuo; Kikuta, Junichi; Sudo, Takao et al.

Scientific Reports, 2020, 10(1), 13480

Number of Access:1,412（2025-09-29 10:04 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93166

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Title	Development of an intravital imaging system for the synovial tissue reveals the dynamics of CTLA-4 Ig in vivo
Creator	NRID 1000030773048 1000030773048 CreatorName Hasegawa, Tetsuo
	NRID 1000060710069 1000060710069 researchmap permalink jkikuta jkikuta Scopus Author ID 36637603800 36637603800 CreatorName Kikuta, Junichi
	NRID 1000080631184 1000080631184 researchmap permalink kik kik Scopus Author ID 36497716100 36497716100 CreatorName Sudo, Takao
	NRID 1000010880106 1000010880106 ORCID 0000-0002-3973-9529 0000-0002-3973-9529 researchmap permalink erika-ys erika-ys CreatorName Yamashita, Erika
	NRID 1000030432462 1000030432462 ORCID 0000-0003-3861-6444 0000-0003-3861-6444 researchmap permalink ssenoo ssenoo Scopus Author ID 57214748425 57214748425 CreatorName Seno, Shigeto
	NRID 1000050179610 1000050179610 CreatorName Takeuchi, Tsutomu
	NRID 1000010324758 1000010324758 researchmap permalink read0076684 read0076684 Scopus Author ID 35074093500 35074093500 CreatorName Ishii, Masaru
Description	Hasegawa T., Kikuta J., Sudo T., et al. Development of an intravital imaging system for the synovial tissue reveals the dynamics of CTLA-4 Ig in vivo. Scientific Reports 10, 13480 (2020); https://doi.org/10.1038/s41598-020-70488-y.
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.
Publisher	Nature Research
Source Title	Scientific Reports
Volume (Issue)	10(1)
Page	13480
Date of Issued	2020-08-10
Language	English
Handle URL	https://hdl.handle.net/11094/93166
eISSN	20452322
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41598-020-70488-y
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Scientific Reports. 2020, 10(1), p. 13480
DC.title	Development of an intravital imaging system for the synovial tissue reveals the dynamics of CTLA-4 Ig in vivo
DC.creator	Hasegawa, Tetsuo
	Kikuta, Junichi
	Sudo, Takao
	Yamashita, Erika
	Seno, Shigeto
	Takeuchi, Tsutomu
	Ishii, Masaru
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2020-08-10
DC.identifier	https://doi.org/10.1038/s41598-020-70488-y
DC.description	Hasegawa T., Kikuta J., Sudo T., et al. Development of an intravital imaging system for the synovial tissue reveals the dynamics of CTLA-4 Ig in vivo. Scientific Reports 10, 13480 (2020); https://doi.org/10.1038/s41598-020-70488-y.
DCTERMS.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.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	93166
citation_title	Development of an intravital imaging system for the synovial tissue reveals the dynamics of CTLA-4 Ig in vivo
citation_author	Hasegawa, Tetsuo
	Kikuta, Junichi
	Sudo, Takao
	Yamashita, Erika
	Seno, Shigeto
	Takeuchi, Tsutomu
	Ishii, Masaru
citation_publisher	Nature Research
citation_language	English
citation_date	2020-08-10
citation_journal_title	Scientific Reports
citation_volume	10
citation_issue	1
citation_firstpage	13480
citation_doi	https://doi.org/10.1038/s41598-020-70488-y
citation_public_url	https://hdl.handle.net/11094/93166

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

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