Role of IL-4 in bone marrow driven dysregulated angiogenesis and age-related macular degeneration
Age-associated sterile inflammation can cause dysregulated choroidal neovascularization (CNV) as age-related macular degeneration (AMD). Intraocular fluid screening of 234 AMD patients identified high levels of IL-4. The purpose of this study was to determine the functional role of IL-4 in CNV forma...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/54257 |
| _version_ | 1811180942845280256 |
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| author | Takashi Baba Dai Miyazaki Kodai Inata Ryu Uotani Hitomi Miyake Shin-ichi Sasaki Yumiko Shimizu Yoshitsugu Inoue Kazuomi Nakamura |
| author_facet | Takashi Baba Dai Miyazaki Kodai Inata Ryu Uotani Hitomi Miyake Shin-ichi Sasaki Yumiko Shimizu Yoshitsugu Inoue Kazuomi Nakamura |
| author_sort | Takashi Baba |
| collection | DOAJ |
| description | Age-associated sterile inflammation can cause dysregulated choroidal neovascularization (CNV) as age-related macular degeneration (AMD). Intraocular fluid screening of 234 AMD patients identified high levels of IL-4. The purpose of this study was to determine the functional role of IL-4 in CNV formation using murine CNV model. Our results indicate that the IL-4/IL-4 receptors (IL4Rs) controlled tube formation and global proangiogenic responses of bone marrow cells. CCR2+ bone marrow cells were recruited to form very early CNV lesions. IL-4 rapidly induces CCL2, which enhances recruitment of CCR2+ bone marrow cells. This in vivo communication, like quorum-sensing, was followed by the induction of IL-4 by the bone marrow cells during the formation of mature CNVs. For CNV development, IL-4 in bone marrow cells are critically required, and IL-4 directly promotes CNV formation mainly by IL-4R. The IL-4/IL-4Rα axis contributes to pathological angiogenesis through communications with bone marrow cells leading to retinal degeneration. |
| first_indexed | 2024-04-11T09:11:48Z |
| format | Article |
| id | doaj.art-6e247087dff2431eb8dd28e7d1056dcb |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:11:48Z |
| publishDate | 2020-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-6e247087dff2431eb8dd28e7d1056dcb2022-12-22T04:32:29ZengeLife Sciences Publications LtdeLife2050-084X2020-05-01910.7554/eLife.54257Role of IL-4 in bone marrow driven dysregulated angiogenesis and age-related macular degenerationTakashi Baba0https://orcid.org/0000-0001-7318-9420Dai Miyazaki1Kodai Inata2Ryu Uotani3Hitomi Miyake4Shin-ichi Sasaki5Yumiko Shimizu6Yoshitsugu Inoue7Kazuomi Nakamura8Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, JapanDivision of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, JapanDivision of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, JapanDivision of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, JapanDivision of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, JapanDivision of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, JapanDivision of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, JapanDivision of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, JapanDivision of Pathological Biochemistry, Department of Biomedical Sciences, Faculty of Medicine, Tottori University, Tottori, JapanAge-associated sterile inflammation can cause dysregulated choroidal neovascularization (CNV) as age-related macular degeneration (AMD). Intraocular fluid screening of 234 AMD patients identified high levels of IL-4. The purpose of this study was to determine the functional role of IL-4 in CNV formation using murine CNV model. Our results indicate that the IL-4/IL-4 receptors (IL4Rs) controlled tube formation and global proangiogenic responses of bone marrow cells. CCR2+ bone marrow cells were recruited to form very early CNV lesions. IL-4 rapidly induces CCL2, which enhances recruitment of CCR2+ bone marrow cells. This in vivo communication, like quorum-sensing, was followed by the induction of IL-4 by the bone marrow cells during the formation of mature CNVs. For CNV development, IL-4 in bone marrow cells are critically required, and IL-4 directly promotes CNV formation mainly by IL-4R. The IL-4/IL-4Rα axis contributes to pathological angiogenesis through communications with bone marrow cells leading to retinal degeneration.https://elifesciences.org/articles/54257age-related macular degenerationchoroidal neovascularizationIL-4angiogenesis |
| spellingShingle | Takashi Baba Dai Miyazaki Kodai Inata Ryu Uotani Hitomi Miyake Shin-ichi Sasaki Yumiko Shimizu Yoshitsugu Inoue Kazuomi Nakamura Role of IL-4 in bone marrow driven dysregulated angiogenesis and age-related macular degeneration eLife age-related macular degeneration choroidal neovascularization IL-4 angiogenesis |
| title | Role of IL-4 in bone marrow driven dysregulated angiogenesis and age-related macular degeneration |
| title_full | Role of IL-4 in bone marrow driven dysregulated angiogenesis and age-related macular degeneration |
| title_fullStr | Role of IL-4 in bone marrow driven dysregulated angiogenesis and age-related macular degeneration |
| title_full_unstemmed | Role of IL-4 in bone marrow driven dysregulated angiogenesis and age-related macular degeneration |
| title_short | Role of IL-4 in bone marrow driven dysregulated angiogenesis and age-related macular degeneration |
| title_sort | role of il 4 in bone marrow driven dysregulated angiogenesis and age related macular degeneration |
| topic | age-related macular degeneration choroidal neovascularization IL-4 angiogenesis |
| url | https://elifesciences.org/articles/54257 |
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