Role of IL-4 in bone marrow driven dysregulated angiogenesis and age-related macular degeneration.

Takashi Baba, Dai Miyazaki, Kodai Inata, Ryu Uotani, Hitomi Miyake, Shin-Ichi Sasaki, Yumiko Shimizu, Yoshitsugu Inoue, Kazuomi Nakamura

eLife 2020 May 05

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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. © 2020, Baba et al.

Citation

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. 2020 May 05;9