Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama 930-0194, Japan.
J Immunol. 2012 Jan 15;188(2):703-13. doi: 10.4049/jimmunol.1101270. Epub 2011 Dec 14.
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.
白细胞介素 5（IL-5）参与多种免疫反应，如寄生虫感染和过敏。IL-5 还通过维持 B-1B 细胞和黏膜 IgA 产生在先天免疫中发挥作用。然而，IL-5 产生细胞的身份尚未得到明确的描述。在本报告中，我们描述了一种 IL-5 报告小鼠的生成，并鉴定了在未致敏小鼠的肠道、腹腔和肺部中存在的产生 IL-5 的非 T 淋巴样细胞。它们与天然辅助细胞、nuocytes 和 Ih2 细胞具有许多共同特征，包括表面抗原和对细胞因子的反应性。然而，这些表型与这些细胞类型中的任何一种都不完全重叠。先天非 T 细胞产生 IL-5 的细胞在肺部的分布最为丰富，它们对 IL-25 和 IL-33 的反应表现为增殖和上调 IL-5 的产生。IL-33 比 IL-25 更有效。这些细胞有助于维持肺部嗜酸性粒细胞的足够数量，并且对于由 IL-25 和 IL-33 介导的嗜酸性粒细胞募集是重要的。鉴于嗜酸性粒细胞被证明具有抗肿瘤活性，我们研究了肺部肿瘤转移，并表明先天产生 IL-5 的细胞在响应肿瘤侵袭时增加，并且它们对嗜酸性粒细胞的调节对于抑制肿瘤转移是至关重要的。IL-5 的遗传阻断或中和会损害嗜酸性粒细胞向肺部的募集，并导致肿瘤转移增加。相反，外源性 IL-5 治疗导致肿瘤转移受到抑制，嗜酸性粒细胞浸润增加。这些新鉴定的先天产生 IL-5 的细胞因此通过肺部嗜酸性粒细胞在肿瘤监测中发挥作用，并可能有助于开发用于癌症的新型免疫疗法。
