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 (CD34⁺CD117⁺α4β7⁺Lin⁻) acquire CD48 and CD52, which define NK progenitors (NKPs) and ILC precursors (ILCPs). Two distinct NK cell subsets were generated in vitro from CD34⁺CD117⁺α4β7⁺Lin⁻CD48⁻CD52⁺ and CD34⁺CD117⁺α4β7⁺Lin⁻CD48⁺CD52⁺ NKPs, respectively. Independent of NKPs, ILCPs exist in the CD34⁺CD117⁺α4β7⁺Lin⁻CD48⁺CD52⁺ subset and give rise to ILC1s, ILC2s, and NCR⁺ ILC3s, whereas CD34⁺CD117⁺α4β7⁺Lin⁻CD48⁺CD52⁻ ILCPs give rise to a distinct subset of ILC3s that have lymphoid tissue inducer (LTi)–like properties. In addition, CD48-expressing CD34⁺CD117⁺α4β7⁺Lin⁻ 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 (ILC) 由共同淋巴祖细胞 (CLP) 发育而来，进一步分化为共同 ILC 祖细胞 (CILP)，后者可产生 I​​LC 和自然杀伤 (NK) 细胞。小鼠 ILC 中间体最近已得到表征，但人类对应物及其发育轨迹尚未确定，这主要是由于两种生物体中缺乏同源表面受体。在这里，我们表明人类 CILP（CD34 ⁺ CD117 ⁺ α4β7 ⁺ Lin ⁻ ）获得 CD48 和 CD52，这定义了 NK 祖细胞（NKP）和 ILC 前体（ILCP）。分别从 CD34 ⁺ CD117 ⁺ α4β7 ⁺ Lin ^- CD48 ^- CD52 ⁺和 CD34 ⁺ CD117 ⁺ α4β7 ⁺ Lin ^- CD48 ⁺ CD52 ⁺ NKP 在体外产生两个不同的 NK 细胞亚群。独立于 NKP，ILCP 存在于 CD34 ⁺ CD117 ⁺ α4β7 ⁺ Lin ⁻ CD48 ⁺ CD52 ⁺子集中，并产生 ILC1、ILC2 和 NCR ⁺ ILC3，而 CD34 ⁺ CD117 ⁺ α4β7 ⁺ Lin ⁻ CD48 ⁺ CD52 ⁻ ILCP 产生 ILC1、ILC2 和 NCR + ILC3。 ILC3 的一个独特子集具有淋巴组织诱导物 (LTi) 样特性。此外，表达CD48的CD34 ⁺ CD117 ⁺ α4β7 ⁺ Lin ^-前体在体内产生组织相关的ILC。 我们还观察到 2B4 与 CD48 的相互作用诱导 ILC2 的分化，并且这些发现共同表明人 ILCP 表达 CD48 调节 ILC 分化。