铁氧化物纳米颗粒（Fe2O3 NPs）在轨道交通系统和广泛的工业生产中产生，对人类健康构成了巨大威胁。然而，对于Fe2O3 NPs在呼吸系统毒性机制方面的研究甚少。Rag1-/-小鼠缺少功能性T和B细胞，经逆行气管内挑战Fe2O3 NPs，以白细胞介素（IL）-33作为第2型固有淋巴细胞（ILC2s）激活剂，观察ILC2s的变化。与野生型（WT）小鼠相比，Rag1-/-小鼠的肺部炎症反应对Fe2O3 NPs得到缓解。肺组织中的炎症细胞和胶原沉积、白细胞数量（中性粒细胞、巨噬细胞和淋巴细胞）、细胞因子水平（如IL-6、IL-13和胸腺基质淋巴样多能细胞生成素[TSLP]）以及下游的Toll样受体（TLR）2、TLR4和Myeloid分化因子（MyD）88等的表达以及核因子（NF）-κB和肿瘤坏死因子（TNF）-α的表达在肺部均有减轻。与对照相比，Fe2O3 NPs显著升高ILC2s的数量，但与IL-33相比，WT和Rag1-/-小鼠的ILC2s数量都要低得多。此外，与WT小鼠相比，Rag1-/-小鼠的ILC2s数量要显著更大。我们的结果表明，Fe2O3 NPs诱导亚慢性肺部炎症主要依赖于T细胞和B细胞而非ILC2s。版权所有 ©2023年Elsevier Ltd发表。

Iron oxide nanoparticles (Fe2O3 NPs), produced in track traffic system and a wide range of industrial production, poses a great threat to human health. However, there is little research about the mechanism of Fe2O3 NPs toxicity on respiratory system. Rag1-/- mice which lack functional T and B cells were intratracheally challenged with Fe2O3 NPs, and interleukin (IL)-33 as an activator of group 2 innate lymphoid cells (ILC2s) to observe ILC2s changes. The lung inflammatory response to Fe2O3 NPs was alleviated in Rag1-/- mice compared with wild type (WT) mice. Infiltration of inflammatory cells and collagen deposition in tissue, leukocyte numbers (neutrophils, macrophages and lymphocytes), cytokine levels, such as IL-6, IL-13 and thymic stromal lymphopoietin (TSLP), and expression of Toll-like receptor (TLR)2, TLR4, and downstream myeloid differentiation factor (MyD)88, nuclear factor (NF)-κB and tumor necrosis factor (TNF)-α were decreased in lungs. Fe2O3 NPs markedly elevated ILC2s compared with the control, but ILC2s numbers were much lower compared with IL-33 in both WT and Rag1-/- mice. Furthermore, ILC2s amounts were strongly greater in Rag1-/- mice than WT mice. Our results suggested that Fe2O3 NPs induced sub-chronic pulmonary inflammation, which is majorly dependent on T cells and B cells rather than ILC2s.Copyright © 2023. Published by Elsevier Ltd.