Aire-expressing ILC3-like cells in the lymph node display potent APC features

Aire-expressing ILC3-like cells in the lymph node display potent APC features
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DOI:
10.1084/jem.20181430
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发表时间:
2019-05-01
影响因子:
15.3
通讯作者:
Filipp, Dominik
Filipp, Dominik
中科院分区:
医学1区
文献类型:
--
作者:
Yamano, Tomoyoshi;Dobes, Jan;Filipp, Dominik

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自身免疫调节因子(Aire)通过促进胸腺上皮细胞中组织抗原的“混杂”表达而对T细胞耐受起重要作用。在外周淋巴器官的罕见细胞中也检测到Aire,但对这些细胞的身份知之甚少。在这里,我们报告说,在淋巴结中的Aire蛋白表达细胞表现出典型的第3组先天淋巴样细胞(ILC3)的特点,如淋巴形态,缺乏“经典”造血谱系标志物,并依赖于ROR γ t。与粘膜引流淋巴结相比,Aire(+)细胞在外周淋巴结的谱系阴性ROR γ t(+)细胞中更常见,显示独特的Aire依赖性转录特征,表达高表面水平的MHCII和共刺激分子,并有效地将内源性表达的模型抗原呈递给CD4(+)。T细胞。这些发现定义了一种具有有效APC特征的新型ILC3样细胞,表明这些细胞在控制T细胞应答中起作用。
The autoimmune regulator (Aire) serves an essential function for T cell tolerance by promoting the "promiscuous" expression of tissue antigens in thymic epithelial cells. Aire is also detected in rare cells in peripheral lymphoid organs, but the identity of these cells is poorly understood. Here, we report that Aire protein-expressing cells in lymph nodes exhibit typical group 3 innate lymphoid cell (ILC3) characteristics such as lymphoid morphology, absence of "classical" hematopoietic lineage markers, and dependence on ROR gamma t. Aire(+) cells are more frequent among lineage-negative ROR gamma t(+) cells of peripheral lymph nodes as compared with mucosa-draining lymph nodes, display a unique Aire-dependent transcriptional signature, express high surface levels of MHCII and costimulatory molecules, and efficiently present an endogenously expressed model antigen to CD4(+). T cells. These findings define a novel type of ILC3-like cells with potent APC features, suggesting that these cells serve a function in the control of T cell responses.