Adoptive transfer of type 1 regulatory T cells suppressed the development of airway hyperresponsiveness in ovalbumin-induced airway inflammation model mice
Adoptive transfer of type 1 regulatory T cells suppressed the development of airway hyperresponsiveness in ovalbumin-induced airway inflammation model mice
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DOI：
10.1016/j.jphs.2019.10.004
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发表时间：
2019-12-01
影响因子：
3.5
通讯作者：
Nabe, Takeshi
中科院分区：
文献类型：
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作者：
Matsuda, Masaya;Doi, Kana;Nabe, Takeshi
1 型调节性 T (Tr1) 细胞是 CD4(+) T 细胞，可产生大量抗炎细胞因子 IL-10。然而，Tr1细胞是否抑制过敏性哮喘尚未完全阐明。在这项研究中，评估了体外诱导的 Tr1 细胞过继转移对过敏性哮喘的影响。将卵清蛋白 (OVA) 致敏的 BALB/c 小鼠的脾细胞与 OVA、IL-21、IL-27 和 TGF-β 一起培养。培养后，通过Dynabeads小鼠CD4和IL-10分泌测定分离产生IL-10的CD4(+)T细胞，并通过流式细胞术进行分析。将纯化的Tr1细胞(IL-10(+)CD4(+)T细胞)静脉注射至OVA致敏的BALB/c小鼠体内。受体小鼠经气管内接受OVA攻击。通过强迫振荡技术评估气道对乙酰甲胆碱的高反应性，然后进行支气管肺泡灌洗（BAL）。几乎所有诱导产生IL-10的CD4+T细胞的干扰素-γ、IL-4、IL-17A和叉头框P3均为阴性，表明这些细胞是Tr1细胞。 Tr1 细胞的过继转移显着抑制了气道高反应性的发展，并增加了 BAL 液中的 IL-5、嗜酸性粒细胞和中性粒细胞。总之，我们证明 Tr1 细胞可以抑制小鼠的过敏性哮喘。 (c) 2019 年作者。由 Elsevier B.V. 代表日本药理学会制作和主办。这是一篇遵循 CC BY-NC-ND 许可证 (http://creativecommons.org/licenses/by-nc-nd/4.0/) 的开放获取文章。
Type 1 regulatory T (Tr1) cells are CD4(+) T cells that produce a large amount of IL-10, an anti-inflammatory cytokine. However, it has not been fully elucidated whether Tr1 cells suppress allergic asthma. In this study, the effects of adoptive transfer of in vitro-induced Tr1 cells on allergic asthma were evaluated. Splenocytes from ovalbumin (OVA)-sensitized BALB/c mice were cultured with OVA, IL-21, IL-27, and TGF-beta. After culture, IL-10-producing CD4(+) T cells were isolated by Dynabeads mouse CD4 and IL-10 secretion assay, and analyzed by flow cytometry. Purified Tr1 cells (IL-10(+) CD4(+) T cells) were intravenously injected into OVA-sensitized BALB/c mice. The recipient mice were intratracheally challenged with OVA. Airway hyperresponsiveness to methacholine was assessed by the forced oscillation technique, followed by bronchoalveolar lavage (BAL). Almost all of the induced IL-10-producing CD4(+) T cells were negative for interferon-gamma, IL-4, IL-17A, and forkhead box P3, suggesting that the cells were Tr1 cells. The adoptive transfer of Tr1 cells significantly suppressed the development of airway hyperresponsiveness, and increases in IL-5, eosinophils, and neutrophils in BAL fluid. In conclusion, we demonstrated that Tr1 cells suppressed allergic asthma in mice. (c) 2019 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).