Terry Fox Laboratory, British Columbia Cancer, Vancouver, BC, Canada.
Interdisciplinary Oncology Program, University of British Columbia, Vancouver, BC, Canada.
Front Immunol. 2021 Jul 9;12:679509. doi: 10.3389/fimmu.2021.679509. eCollection 2021.
Group 2 innate lymphoid cells (ILC2s) are tissue resident in the lung and activated by inhaled allergens epithelial-derived alarmins including IL-33. Activated ILC2s proliferate, produce IL-5 and IL-13, and induce eosinophilic inflammation. Here, we report that intranasal IL-33 or the protease allergen papain administration resulted in increased numbers of ILC2s not only in the lung but also in peripheral blood and liver. Analyses of IL-33 treated parabiosis mice showed that the increase in lung ILC2s was due to proliferation of lung resident ILC2s, whereas the increase in liver ILC2s was due to the migration of activated lung ILC2s. Lung-derived ILC2s induced eosinophilic hepatitis and expression of fibrosis-related genes. Intranasal IL-33 pre-treatment also attenuated concanavalin A-induced acute hepatitis and cirrhosis. These results suggest that activated lung resident ILC2s emigrate from the lung, circulate, settle in the liver and promote type 2 inflammation and attenuate type 1 inflammation.
2 型固有淋巴细胞（ILC2s）是肺组织中的固有细胞，可被吸入的过敏原和上皮细胞衍生的警报素（如 IL-33）激活。激活的 ILC2s 增殖，产生 IL-5 和 IL-13，并诱导嗜酸性粒细胞炎症。在这里，我们报告鼻内 IL-33 或蛋白酶过敏原木瓜蛋白酶给药不仅导致肺部，还导致外周血和肝脏中 ILC2s 数量增加。对接受侧侧连接处理的 IL-33 治疗的同基因小鼠进行分析表明，肺 ILC2s 的增加是由于肺驻留的 ILC2s 的增殖，而肝脏 ILC2s 的增加是由于激活的肺 ILC2s 的迁移。肺来源的 ILC2s 诱导嗜酸性粒细胞性肝炎和纤维化相关基因的表达。鼻内 IL-33 预处理也可减轻伴刀豆球蛋白 A 诱导的急性肝炎和肝硬化。这些结果表明，激活的肺固有驻留的 ILC2s 从肺部迁出，循环，定居在肝脏，并促进 2 型炎症，减轻 1 型炎症。
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