美国国立卫生研究院Avinash Bhandoola等合作研究组在研究中取得进展。他们揭示了不同的发育途径产生功能不同的自然杀伤细胞群。这一研究成果发表在2024年6月13日出版的国际学术期刊《自然—免疫学》上。

小组确定了一个自然杀伤谱系偏向的祖细胞群体，称为早期自然杀伤祖细胞(ENKPs)，它独立于先天淋巴样细胞(ILCPs)的共同前体发育成自然杀伤细胞。早期自然杀伤祖细胞来源的自然杀伤细胞(ENKP_NK细胞)和先天淋巴样细胞来源的自然杀伤细胞(ILCP_NK细胞)在转录上存在差异。课题组人员设计了表面标记物的组合来鉴定野生型小鼠中高度富集的ENKP_NK和ILCP_NK细胞群。

此外，Ly49H⁺ 自然杀伤细胞对单核巨细胞病毒感染的反应主要来自ENKPs，而ILCP_NK细胞在感染沙门氏菌和单纯疱疹病毒后能更好地产生IFNγ。人CD56^dim和CD56^bright 自然杀伤细胞在转录上分别与ENKP_NK细胞和ILCP_NK细胞相似。他们的发现确立了自然杀伤细胞发育的两种途径的存在，这两种途径在小鼠中产生功能不同的NK细胞亚群，并进一步表明这些途径可能在人类中保守。

据了解，自然杀伤(NK)细胞的功能是消灭病毒感染细胞或肿瘤细胞。

附：英文原文

Title: Distinct developmental pathways generate functionally distinct populations of natural killer cells

Author: Ding, Yi, Lavaert, Marieke, Grassmann, Simon, Band, Victor I., Chi, Liang, Das, Arundhoti, Das, Sumit, Harly, Christelle, Shissler, Susannah C., Malin, Justin, Peng, Dingkang, Zhao, Yongge, Zhu, Jinfang, Belkaid, Yasmine, Sun, Joseph C., Bhandoola, Avinash

Issue&Volume: 2024-06-13

Abstract: Natural killer (NK) cells function by eliminating virus-infected or tumor cells. Here we identified an NK-lineage-biased progenitor population, referred to as early NK progenitors (ENKPs), which developed into NK cells independently of common precursors for innate lymphoid cells (ILCPs). ENKP-derived NK cells (ENKP_NK cells) and ILCP-derived NK cells (ILCP_NK cells) were transcriptionally different. We devised combinations of surface markers that identified highly enriched ENKP_NK and ILCP_NK cell populations in wild-type mice. Furthermore, Ly49H+ NK cells that responded to mouse cytomegalovirus infection primarily developed from ENKPs, whereas ILCP_NK cells were better IFNγ producers after infection with Salmonella and herpes simplex virus. Human CD56dim and CD56bright NK cells were transcriptionally similar to ENKP_NK cells and ILCP_NK cells, respectively. Our findings establish the existence of two pathways of NK cell development that generate functionally distinct NK cell subsets in mice and further suggest these pathways may be conserved in humans.

DOI: 10.1038/s41590-024-01865-2

Source: https://www.nature.com/articles/s41590-024-01865-2