Respiratory Medicine Unit and NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
Translational Gastroenterology Unit and Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
Mucosal Immunol. 2022 May;15(5):990-999. doi: 10.1038/s41385-022-00543-6. Epub 2022 Jul 9.
Type 2 immunity mediates the immune responses against parasites and allergic stimuli. Evidence from studies of cell lines and animals implies that neuromedin U (NmU) acts as a pro-inflammatory mediator of type 2 inflammation. However, the role of NmU in human type 2 immunity remains unclear. Here we investigated the expression of NmU in human blood and airways, and the expression of NmU receptors by human immune cells in blood and lung tissue. We detected human NmU (hNmU-25) in blood and airways with higher concentrations in the latter. NmU receptor 1 (NmUR1) was expressed by most human immune cells with higher levels in type 2 cells including type 2 T helpers, type 2 cytotoxic T cells, group-2 innate lymphoid cells and eosinophils, and was upregulated in lung-resident and activated type 2 cells. We also assessed the effects of NmU in these cells. hNmU-25 elicited type 2 cytokine production by type 2 lymphocytes and induced cell migration, including eosinophils. hNmU-25 also enhanced the type 2 immune response to other stimuli, particularly prostaglandin D. These results indicate that NmU could contribute to the pathogenic processes of type 2 immunity-mediated diseases in humans via its pro-inflammatory effects on type 2 lymphocytes and eosinophils.
2 型免疫介导了针对寄生虫和变应原的免疫反应。来自细胞系和动物研究的证据表明，神经肽 U（NmU）是 2 型炎症的促炎介质。然而，NmU 在人类 2 型免疫中的作用尚不清楚。在这里，我们研究了 NmU 在人血液和气道中的表达，以及人免疫细胞在血液和肺组织中 NmU 受体的表达。我们在血液和气道中检测到人类 NmU（hNmU-25），后者的浓度更高。NmU 受体 1（NmUR1）表达于大多数人类免疫细胞，2 型细胞包括 2 型 T 辅助细胞、2 型细胞毒性 T 细胞、2 型先天淋巴样细胞和嗜酸性粒细胞中的表达水平更高，并且在肺驻留和激活的 2 型细胞中上调。我们还评估了 NmU 在这些细胞中的作用。hNmU-25 可诱导 2 型淋巴细胞产生 2 型细胞因子，并诱导细胞迁移，包括嗜酸性粒细胞。hNmU-25 还增强了 2 型淋巴细胞对其他刺激物，特别是前列腺素 D 的 2 型免疫反应。这些结果表明，NmU 通过其对 2 型淋巴细胞和嗜酸性粒细胞的促炎作用，可能有助于人类 2 型免疫介导疾病的发病机制。
