Granulocyte macrophage colony-stimulating factor-induced macrophages of individuals with autism spectrum disorder adversely affect neuronal dendrites through the secretion of pro-inflammatory cytokines

• 資料種別: 博士論文
• タイトル: Granulocyte macrophage colony-stimulating factor-induced macrophages of individuals with autism spectrum disorder adversely affect neuronal dendrites through the secretion of pro-inflammatory cytokines
• 著者・編者: Takada, Ryohei; Toritsuka, Michihiro; Yamauchi, Takahira; Ishida, Rio; Kayashima, Yoshinori; Nishi, Yuki; Ishikawa, Mitsuru; Yamamuro, Kazuhiko; Ikehara, Minobu; Komori, Takashi; Noriyama, Yuki; Kamikawa, Kohei; Saito, Yasuhiko; Okano, Hideyuki; Makinodan, Manabu
• 著者標目: Takada, Ryohei; Toritsuka, Michihiro; Yamauchi, Takahira; Ishida, Rio; Kayashima, Yoshinori; Nishi, Yuki; Ishikawa, Mitsuru; Yamamuro, Kazuhiko; Ikehara, Minobu; Komori, Takashi; Noriyama, Yuki; Kamikawa, Kohei; Saito, Yasuhiko; Okano, Hideyuki; Makinodan, Manabu
• 出版事項: BMC
• 出版年月日等: 2024-02
• 出版年（W3CDTF）: 2024-02
• 並列タイトル等: "自閉スペクトラム症者の顆粒球マクロファージコロニー刺激因子誘導マクロファージ は、炎症性サイトカインの分泌を介して、神経細胞の樹状突起に悪影響を及ぼす"
• タイトル（掲載誌）: Molecular autism
• 巻号年月日等（掲載誌）: 15 1
• 掲載巻: 15
• 掲載号: 1
• 掲載ページ: 10-
• ISSN（掲載誌）: ISSN : 2040-2392
• 授与機関名: 奈良県立医科大学
• 授与年月日: 2024-06-26
• 報告番号: 甲第930号
• 学位: 博士（医学）
• 本文の言語コード: eng
• 件名標目: Autism spectrum disorder; Human iPS cell; Macrophage; Interleukin-1α; Tumor necrosis factor-α; Dendrite
• 対象利用者: 一般
• 一般注記: 出版タイプ： VoR; type:Thesis; Background: A growing body of evidence suggests that immune dysfunction and inflammation in the peripheral tissues as well as the central nervous system are associated with the neurodevelopmental deficits observed in autism spectrum disorder (ASD). Elevated expression of pro-inflammatory cytokines in the plasma, serum, and peripheral blood mononuclear cells of ASD has been reported. These cytokine expression levels are associated with the severity of behavioral impairments and symptoms in ASD. In a prior study, our group reported that tumor necrosis factor-α (TNF-α) expression in granulocyte-macrophage colony-stimulating factor-induced macrophages (GM-CSF MΦ) and the TNF-α expression ratio in GM-CSF MΦ/M-CSF MΦ (macrophage colony-stimulating factor-induced macrophages) was markedly higher in individuals with ASD than in typically developed (TD) individuals. However, the mechanisms of how the macrophages and the highly expressed cytokines affect neurons remain to be addressed. Methods: To elucidate the effect of macrophages on human neurons, we used a co-culture system of control human-induced pluripotent stem cell-derived neurons and differentiated macrophages obtained from the peripheral blood mononuclear cells of five TD individuals and five individuals with ASD. All participants were male and ethnically Japanese. Results: Our results of co-culture experiments showed that GM-CSF MΦ affect the dendritic outgrowth of neurons through the secretion of pro-inflammatory cytokines, interleukin-1α and TNF-α. Macrophages derived from individuals with ASD exerted more severe effects than those derived from TD individuals. Limitations: The main limitations of our study were the small sample size with a gender bias toward males, the use of artificially polarized macrophages, and the inability to directly observe the interaction between neurons and macrophages from the same individuals. Conclusions: Our co-culture system revealed the non-cell autonomous adverse effects of GM-CSF MΦ in individuals with ASD on neurons, mediated by interleukin-1α and TNF-α. These results may support the immune dysfunction hypothesis of ASD, providing new insights into its pathology.; 権利情報：© The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.; identifier:Molecular autism. 2024 Feb, vol.15, no.1, article no.10; identifier:2040-2392; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4387; identifier:Molecular autism, 15(1): 10
• 一次資料へのリンクURL: fulltext; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4387/1/01%e7%94%b2930%e6%9c%ac%e6%96%87.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4387/2/02%e7%94%b2930%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4387/3/03%e7%94%b2930%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf
• オンライン閲覧公開範囲: インターネット公開
• 関連情報（DOI）: 10.1186/s13229-024-00589-2; https://doi.org/10.1186/s13229-024-00589-2
• 連携機関・データベース: 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• 提供元機関・データベース: 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU