Innate IL-13-producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity
Innate IL-13-producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity
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DOI：
10.1016/j.jaci.2011.09.041
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发表时间：
2012-01-01
影响因子：
14.2
通讯作者：
McKenzie, Andrew N. J.
中科院分区：
文献类型：
--
作者：
Barlow, Jillian L.;Bellosi, Agustin;McKenzie, Andrew N. J.
背景：IL-4、IL-5和IL-13被认为是过敏性哮喘反应的中心。以前的工作认为这些细胞因子的主要来源是CD4(+)T(H)2细胞。然而，最近的研究表明，其他先天产生的2型细胞因子可能也同样重要。目的：核细胞是一种新的产生IL-13的先天细胞群，在巴西拟青虫感染的保护性免疫中起关键作用。有鉴于此，我们研究了白细胞在实验性变态反应性哮喘中的潜在存在及其功能重要性。方法：我们建立了IL4(+/EGFP)IL13(+/番茄)双报告小鼠，以研究变态反应性炎症过程中细胞因子的产生。我们过继转移了先天产生IL-13的细胞，以探讨它们在呼吸道高反应性(AHR)中的作用。结果：我们发现变应原诱导的核细胞渗透到肺中，是IL-13的主要先天来源。肺中的CD4(+)T细胞几乎只表达IL-13，而产生IL-4的T细胞仅限于引流的淋巴结。鼻腔注射IL-25或IL-33可诱导BAL液中产生IL-13的有核细胞。值得注意的是，将野生型核细胞而不是IL13(-/-)核细胞过继转移到IL13(-/-)小鼠体内，恢复了呼吸道阻力和肺细胞浸润。结论：这些发现表明，核细胞是变态反应性肺部炎症中的一种新的细胞类型，在没有产生IL-13的CD4(+)T细胞的情况下，可以直接诱导AHR。这些数据强调，在未来过敏性哮喘治疗的发展中，中性粒细胞是一个重要的新考虑因素。(《过敏与免疫杂志》2012；129：191-8。)
Background: IL-4, IL-5, and IL-13 are thought to be central to the allergic asthmatic response. Previous work supposed that the essential source of these cytokines was CD4(+) T(H)2 cells. However, more recent studies have suggested that other innate production of type 2 cytokines might be as important.Objectives: Nuocytes are a novel population of IL-13-producing innate cells, which are critical for protective immunity in Nippostrongylus brasiliensis infection. Given this, we investigated the potential existence and functional importance of nuocytes in experimental allergic asthma.Methods: We generated Il4(+/eGFP)Il13(+/Tomato) dual-reporter mice to study cytokine-producing cells during allergic inflammation. We adoptively transferred innate IL-13-producing cells to investigate their role in airways hyperreactivity (AHR).Results: We show that allergen-induced nuocytes infiltrate the lung and are a major innate source of IL-13. CD4(+) T cells in the lung almost exclusively express only IL-13, whereas IL-4-producing T cells were restricted to the draining lymph nodes. Intranasal administration of IL-25 or IL-33 induced IL-13-producing nuocytes in the BAL fluid. Strikingly, adoptive transfer of wild-type nuocytes, but not Il13(-/-) nuocytes, into Il13(-/-) mice, which are normally resistant to IL-25-induced AHR, restored airways resistance and lung cell infiltration.Conclusions: These findings identify nuocytes as a novel cell type in allergic lung inflammation and an innate source of IL-13 that can directly induce AHR in the absence of IL-13-producing CD4(+) T cells. These data highlight nuocytes as an important new consideration in the development of future allergic asthma therapy. (J Allergy Clin Immunol 2012; 129: 191-8.)