Department of Pediatric, Division of Children's Cancer and Blood Disorders, University of Colorado and Children's Hospital of Colorado, Research Complex 1, North Tower, 12800 E. 19th Ave., Mail Stop 8302, Room P18-4108, Aurora, CO 80045, USA.
Sci Immunol. 2020 Nov 20;5(53). doi: 10.1126/sciimmunol.aay4218.
Innate lymphoid cells (ILCs) develop from common lymphoid progenitors (CLPs), which further differentiate into the common ILC progenitor (CILP) that can give rise to both ILCs and natural killer (NK) cells. Murine ILC intermediates have recently been characterized, but the human counterparts and their developmental trajectories have not yet been identified, largely due to the lack of homologous surface receptors in both organisms. Here, we show that human CILPs (CD34CD117α4β7Lin) acquire CD48 and CD52, which define NK progenitors (NKPs) and ILC precursors (ILCPs). Two distinct NK cell subsets were generated in vitro from CD34CD117α4β7LinCD48CD52 and CD34CD117α4β7LinCD48CD52 NKPs, respectively. Independent of NKPs, ILCPs exist in the CD34CD117α4β7LinCD48CD52 subset and give rise to ILC1s, ILC2s, and NCR ILC3s, whereas CD34CD117α4β7LinCD48CD52 ILCPs give rise to a distinct subset of ILC3s that have lymphoid tissue inducer (LTi)-like properties. In addition, CD48-expressing CD34CD117α4β7Lin precursors give rise to tissue-associated ILCs in vivo. We also observed that the interaction of 2B4 with CD48 induced differentiation of ILC2s, and together, these findings show that expression of CD48 by human ILCPs modulates ILC differentiation.
先天淋巴细胞 (ILCs) 由共同淋巴祖细胞 (CLPs) 发育而来，进一步分化为共同 ILC 祖细胞 (CILP)，可分化为 ILCs 和自然杀伤 (NK) 细胞。鼠类 ILC 中间产物最近已被鉴定，但人类对应物及其发育轨迹尚未确定，这主要是由于两个生物体中缺乏同源表面受体。在这里，我们表明人类 CILPs (CD34CD117α4β7Lin) 获得了 CD48 和 CD52，这定义了 NK 祖细胞 (NKPs) 和 ILC 前体 (ILCPs)。从 CD34CD117α4β7LinCD48CD52 和 CD34CD117α4β7LinCD48CD52 NKPs 分别体外生成了两个不同的 NK 细胞亚群。独立于 NKPs，ILCPs 存在于 CD34CD117α4β7LinCD48CD52 亚群中，并分化为 ILC1s、ILC2s 和 NCR ILC3s，而 CD34CD117α4β7LinCD48CD52 ILCPs 分化为具有淋巴组织诱导 (LTi)-样特性的独特 ILC3 亚群。此外，表达 CD48 的 CD34CD117α4β7Lin 前体在体内产生组织相关的 ILCs。我们还观察到 2B4 与 CD48 的相互作用诱导了 ILC2 的分化，这些发现共同表明人类 ILC 前体 CD48 的表达调节了 ILC 的分化。
