Department of Experimental Medicine, University of Genova, Via LB Alberti 2, 16132 Genova, Italy; UOC Immunologia, IRCCS-AOU-San Martino-IST, L.go R. Benzi 10, 16132 Genova, Italy.
Innate Immunity, Deutsches Rheuma Forschungszentrum (DRFZ) Berlin, Leibniz-Gemeinschaft, Charitéplatz 1, 10117 Berlin, Germany.
Immunity. 2014 Dec 18;41(6):988-1000. doi: 10.1016/j.immuni.2014.11.010. Epub 2014 Nov 28.
Group 3 innate lymphoid cells (ILC3s) are defined by the expression of the transcription factor RORγt, which is selectively required for their development. The lineage-specified progenitors of ILC3s and their site of development after birth remain undefined. Here we identified a population of human CD34(+) hematopoietic progenitor cells (HPCs) that express RORγt and share a distinct transcriptional signature with ILC3s. RORγt(+)CD34(+) HPCs were located in tonsils and intestinal lamina propria (LP) and selectively differentiated toward ILC3s. In contrast, RORγt(-)CD34(+) HPCs could differentiate to become either ILC3s or natural killer (NK) cells, with differentiation toward ILC3 lineage determined by stem cell factor (SCF) and aryl hydrocarbon receptor (AhR) signaling. Thus, we demonstrate that in humans RORγt(+)CD34(+) cells are lineage-specified progenitors of IL-22(+) ILC3s and propose that tonsils and intestinal LP, which are enriched both in committed precursors and mature ILC3s, might represent preferential sites of ILC3 lineage differentiation.
第三组固有淋巴细胞 (ILC3) 被定义为转录因子 RORγt 的表达，其选择性地需要其发育。ILC3 的谱系指定祖细胞及其出生后的发育部位仍未定义。在这里，我们鉴定了一群人 CD34(+) 造血祖细胞 (HPC)，其表达 RORγt 并与 ILC3 具有独特的转录特征。RORγt(+)CD34(+) HPC 位于扁桃体和肠固有层 (LP) 中，并选择性地向 ILC3 分化。相比之下，RORγt(-)CD34(+) HPC 可以分化为 ILC3 或自然杀伤 (NK) 细胞，向 ILC3 谱系的分化由干细胞因子 (SCF) 和芳基烃受体 (AhR) 信号决定。因此，我们证明在人类中，RORγt(+)CD34(+) 细胞是 IL-22(+) ILC3 的谱系指定祖细胞，并提出扁桃体和肠 LP 富含成熟的 ILC3 和定向 ILC3 谱系分化的祖细胞，可能代表 ILC3 谱系分化的优先部位。
