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

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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.
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Category
学術雑誌論文 Journal Article