Cupedo Tom, Crellin Natasha K, Papazian Natalie, Rombouts Elwin J, Weijer Kees, Grogan Jane L, Fibbe Willem E, Cornelissen Jan J, Spits Hergen
Department of Hematology, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands.
Nat Immunol. 2009 Jan;10(1):66-74. doi: 10.1038/ni.1668. Epub 2008 Nov 23.
The human body contains over 500 individual lymph nodes, yet the biology of their formation is poorly understood. Here we identify human lymphoid tissue-inducer cells (LTi cells) as lineage-negative RORC+ CD127+ cells with the functional ability to interact with mesenchymal cells through lymphotoxin and tumor necrosis factor. Human LTi cells were committed natural killer (NK) cell precursors that produced interleukin 17 (IL-17) and IL-22. In vitro, LTi cells gave rise to RORC+ CD127+ NK cells that retained the ability to produce IL-17 and IL-22. Postnatally, similar populations of LTi cell-like cells and RORC+ CD127+ NK cells were present in tonsils, and both secreted IL-17 and IL-22 but no interferon-gamma. Our data indicate that lymph node organogenesis is controlled by an NK cell precursor population with adaptive immune features and demonstrate a previously unappreciated link between the innate and adaptive immune systems.
人体含有500多个单个淋巴结，但其形成的生物学机制却鲜为人知。在此，我们将人类淋巴组织诱导细胞（LTi细胞）鉴定为谱系阴性RORC + CD127 +细胞，其具有通过淋巴毒素和肿瘤坏死因子与间充质细胞相互作用的功能能力。人类LTi细胞是产生白细胞介素17（IL-17）和IL-22的天然杀伤（NK）细胞前体。在体外，LTi细胞产生RORC + CD127 + NK细胞，这些细胞保留了产生IL-17和IL-22的能力。出生后，扁桃体中存在类似的LTi细胞样细胞群和RORC + CD127 + NK细胞，两者均分泌IL-17和IL-22，但不分泌干扰素-γ。我们的数据表明，淋巴结器官发生受具有适应性免疫特征的NK细胞前体群体控制，并证明了先天免疫系统和适应性免疫系统之间以前未被认识到的联系。
