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Abstract：
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.
摘要：
先天淋巴细胞（ILC）从常见的淋巴祖细胞（CLP）发展而来，进一步分化为共同的ILC祖细胞（CILP），可以产生ILC和自然杀伤（NK）细胞。最近对小鼠ILC中间体进行了表征，但是人类的同伴及其发展轨迹尚未确定，很大程度上是由于两种生物都缺乏同源表面受体。这里,我们显示humanCILP（CD34CD117α4β7Lin-）获得CD48和CD52，它们定义了NK祖细胞（NKPs）和ILC前体（ILCP）。从CD34+CD117+α4β7+Lin-CD48-CD52+和CD34+CD117+α4β7+Lin-CD48+CD52+NKPs体外产生两个不同的NK细胞亚群，分别。独立于NKP，ILCP存在于CD34+CD117+α4β7+Lin-CD48+CD52+亚群中,ILC2s,和NCR+ILC3，而CD34+CD117+α4β7+Lin-CD48+CD52-ILCP产生具有淋巴组织诱导物(LTi)样特性的不同ILC3亚群。此外,表达CD48的CD34+CD117+α4β7+Lin-前体在体内产生组织相关ILC。我们还观察到2B4与CD48的相互作用诱导了ILC2s的分化，一起,这些发现表明，人ILCPs表达CD48可调节ILC分化。
