Neuromedin U promotes human type 2 immune responses.

Neuromedin U promotes human type 2 immune responses.
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DOI:
10.1038/s41385-022-00543-6
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发表时间:
2022-05
期刊:
影响因子:
8
通讯作者:
Xue, Luzheng
Xue, Luzheng
中科院分区:
医学1区
文献类型:
--
作者:
Ye, Yuan;Luo, Jian;Zeng, Ni;Jiang, Shan;Chen, Wentao;Hoyle, Ryan D.;Klenerman, Paul;Pavord, Ian D.;Xue, Luzheng

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2型免疫介导对寄生虫和过敏刺激的免疫反应。来自细胞系和动物研究的证据表明,神经质素U (NmU)作为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。本文研究了NmU在人血液和气道中的表达,以及NmU受体在人血液和肺组织中免疫细胞的表达。我们在血液和气道中检测到人类NmU (hNmU-25),后者浓度较高。NmU受体1 (NmUR1)在大多数人类免疫细胞中表达,在包括2型T辅助细胞、2型细胞毒性T细胞、2组先天淋巴样细胞和嗜酸性粒细胞在内的2型细胞中表达水平较高,在肺驻留和活化的2型细胞中表达上调。我们还评估了NmU在这些细胞中的作用。hNmU-25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还增强了对其他刺激的2型免疫反应,特别是前列腺素D2。这些结果表明,NmU可能通过其对2型淋巴细胞和嗜酸性粒细胞的促炎作用参与人类2型免疫介导疾病的致病过程。
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 D2. 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.
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