美国加州大学洛杉矶分校Timothy E. O’Sullivan研究小组发现转录因子Fli1在病毒感染过程中限制记忆前体自然杀伤（NK）细胞的形成。相关论文于2022年3月14日在线发表在《自然—免疫学》杂志上。

利用单细胞RNA测序，研究人员在小鼠巨细胞病毒感染后发现了两个不同的效应NK细胞（NK_eff）群体。Ly6C^-记忆前体（MP）NK细胞在收缩期以Bcl2依赖性的方式显示出增强的存活率，并分化成Ly6C⁺记忆NK细胞。与Ly6C⁺ NK_eff细胞相比，MP NK细胞表现出不同的转录和表观遗传特征，其核心表观遗传特征与MP CD8⁺ T细胞共享，富含ETS1和Fli1 DNA结合模体。Fli1在体内被STAT5信号诱导，病毒感染后早期效应NK细胞中促凋亡因子Bim的水平增加。这些结果表明，在病毒感染期间，由转录因子Fli1控制的NK细胞内在检查点通过调节早期效应NK细胞的适应性限制MP NK的形成。

据介绍，NK细胞是先天性淋巴细胞，具有适应性免疫的特征，如记忆形成。然而，NK细胞持续形成记忆细胞的分子机制还不是很清楚。

附：英文原文

Title: The transcription factor Fli1 restricts the formation of memory precursor NK cells during viral infection

Author: Riggan, Luke, Ma, Feiyang, Li, Joey H., Fernandez, Elizabeth, Nathanson, David A., Pellegrini, Matteo, OSullivan, Timothy E.

Issue&Volume: 2022-03-14

Abstract: Natural killer (NK) cells are innate lymphocytes that possess traits of adaptive immunity, such as memory formation. However, the molecular mechanisms by which NK cells persist to form memory cells are not well understood. Using single-cell RNA sequencing, we identified two distinct effector NK cell (NKeff) populations following mouse cytomegalovirus infection. Ly6C– memory precursor (MP) NK cells showed enhanced survival during the contraction phase in a Bcl2-dependent manner, and differentiated into Ly6C+ memory NK cells. MP NK cells exhibited distinct transcriptional and epigenetic signatures compared with Ly6C+ NKeff cells, with a core epigenetic signature shared with MP CD8+ T cells enriched in ETS1 and Fli1 DNA-binding motifs. Fli1 was induced by STAT5 signaling ex vivo, and increased levels of the pro-apoptotic factor Bim in early effector NK cells following viral infection. These results suggest that a NK cell-intrinsic checkpoint controlled by the transcription factor Fli1 limits MP NK formation by regulating early effector NK cell fitness during viral infection.

DOI: 10.1038/s41590-022-01150-0

Source: https://www.nature.com/articles/s41590-022-01150-0