Shikhagaie Medya Mara, Björklund Åsa K, Mjösberg Jenny, Erjefält Jonas S, Cornelissen Anne S, Ros Xavier Romero, Bal Suzanne M, Koning Jasper J, Mebius Reina E, Mori Michiko, Bruchard Melanie, Blom Bianca, Spits Hergen
Department of Experimental Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Cell Rep. 2017 Feb 14;18(7):1761-1773. doi: 10.1016/j.celrep.2017.01.063.
Here, we characterize a subset of ILC3s that express Neuropilin1 (NRP1) and are present in lymphoid tissues, but not in the peripheral blood or skin. NRP1 group 3 innate lymphoid cells (ILC3s) display in vitro lymphoid tissue inducer (LTi) activity. In agreement with this, NRP1 ILC3s are mainly located in proximity to high endothelial venules (HEVs) and express cell surface molecules involved in lymphocyte migration in secondary lymphoid tissues via HEVs. NRP1 was also expressed on mouse fetal LTi cells, indicating that NRP1 is a conserved marker for LTi cells. Human NRP1 ILC3s are primed cells because they express CD45RO and produce higher amounts of cytokines than NRP1 cells, which express CD45RA. The NRP1 ligand vascular endothelial growth factor A (VEGF-A) served as a chemotactic factor for NRP1 ILC3s. NRP1 ILC3s are present in lung tissues from smokers and patients with chronic obstructive pulmonary disease, suggesting a role in angiogenesis and/or the initiation of ectopic pulmonary lymphoid aggregates.
在这里，我们鉴定了一群表达神经纤毛蛋白1（NRP1）的3型固有淋巴细胞（ILC3s），它们存在于淋巴组织中，但外周血和皮肤中没有。NRP1⁺ 3型固有淋巴细胞（ILC3s）在体外表现出淋巴组织诱导细胞（LTi）活性。与此一致的是，NRP1⁺ ILC3s主要位于高内皮小静脉（HEVs）附近，并表达参与淋巴细胞通过HEVs在二级淋巴组织中迁移的细胞表面分子。NRP1在小鼠胎儿LTi细胞上也有表达，这表明NRP1是LTi细胞的一个保守标志物。人NRP1⁺ ILC3s是致敏细胞，因为它们表达CD45RO，并且比表达CD45RA的NRP1⁻细胞产生更多的细胞因子。NRP1的配体血管内皮生长因子A（VEGF-A）作为NRP1⁺ ILC3s的趋化因子。NRP1⁺ ILC3s存在于吸烟者和慢性阻塞性肺疾病患者的肺组织中，提示其在血管生成和/或异位肺淋巴聚集起始中发挥作用。
