Identification of Innate IL-5-Producing Cells and Their Role in Lung Eosinophil Regulation and Antitumor Immunity
Identification of Innate IL-5-Producing Cells and Their Role in Lung Eosinophil Regulation and Antitumor Immunity
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DOI：
10.4049/jimmunol.1101270
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发表时间：
2012-01-15
影响因子：
4.4
通讯作者：
Takatsu, Kiyoshi
中科院分区：
文献类型：
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作者：
Ikutani, Masashi;Yanagibashi, Tsutomu;Takatsu, Kiyoshi
IL-5参与多种免疫反应，如蠕虫感染和过敏。IL-5还通过维持B-1B细胞和粘膜免疫球蛋白A的产生，在先天免疫中发挥作用。然而，产生IL-5的细胞的特性还没有明确的描述。在这篇报道中，我们描述了IL-5报告小鼠的产生，并鉴定了幼小鼠肠道、腹膜腔和肺中存在的产生IL-5的非T淋巴样细胞。它们与自然辅助细胞、有核细胞和Ih2细胞有许多共同的特征，包括表面抗原和对细胞因子的反应性。然而，这些表型并不与这些细胞类型中的任何一种完全重叠。先天非T-IL-5产生细胞主要分布在肺内，在IL-25和IL-33刺激下增殖和上调IL-5的产生。IL-33的疗效优于IL-25。这些细胞有助于维持足够数量的肺嗜酸性粒细胞，并对IL-25和IL-33介导的嗜酸性粒细胞募集起重要作用。鉴于嗜酸性粒细胞被证明具有抗肿瘤活性，我们研究了肺癌的转移，发现天然的IL-5产生细胞随着肿瘤的侵袭而增加，它们对嗜酸性粒细胞的调节是抑制肿瘤转移的关键。基因阻断或中和IL-5会损害嗜酸性粒细胞向肺内的募集，并导致肿瘤转移增加。相反，外源性IL-5治疗可抑制肿瘤转移，增加嗜酸性粒细胞的浸润。因此，这些新发现的天然IL-5产生细胞通过肺嗜酸性粒细胞在肿瘤监测中发挥作用，并可能有助于开发新的癌症免疫疗法。免疫学杂志，2012,188：703-713。
IL-5 is involved in a number of immune responses such as helminth infection and allergy. IL-5 also plays roles in innate immunity by maintaining B-1 B cells and mucosal IgA production. However, the identity of IL-5-producing cells has not been unambiguously characterized. In this report, we describe the generation of an IL-5 reporter mouse and identify IL-5-producing non-T lymphoid cells that reside in the intestine, peritoneal cavity, and lungs in naive mice. They share many characteristics with natural helper cells, nuocytes, and Ih2 cells, including surface Ags and responsiveness to cytokines. However, these phenotypes do not completely overlap with any particular one of these cell types. Innate non-T IL-5-producing cells localized most abundantly in the lung and proliferated and upregulated IL-5 production in response to IL-25 and IL-33. IL-33 was more effective than IL-25. These cells contribute to maintaining sufficient numbers of lung eosinophils and are important for eosinophil recruitment mediated by IL-25 and IL-33. Given that eosinophils are shown to possess antitumor activity, we studied lung tumor metastasis and showed that innate IL-5-producing cells were increased in response to tumor invasion, and their regulation of eosinophils is critical to suppress tumor metastasis. Genetic blockade or neutralization of IL-5 impaired eosinophil recruitment into the lung and resulted in increased tumor metastasis. Conversely, exogenous IL-5 treatment resulted in suppressed tumor metastasis and augmented eosinophil infiltration. These newly identified innate IL-5-producing cells thus play a role in tumor surveillance through lung eosinophils and may contribute to development of novel immunotherapies for cancer. The Journal of Immunology, 2012, 188: 703-713.