生物
造血
先天免疫系统
淋巴细胞生成
细胞分化
干细胞
免疫系统
信号转导
髓样
免疫学
细胞信号
T细胞
作者
Dejene M. Tufa,Ashley Yingst,George Devon Trahan,Tyler Shank,Dallas Jones,Seonhui Shim,Jessica Lake,Kevin Winkler,Laura Cobb,Renee Woods,Kenneth L. Jones,Michael R. Verneris
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2020-11-20
卷期号:5 (53)
被引量:4
标识
DOI:10.1126/sciimmunol.aay4218
摘要
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.
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