德国维尔茨堡系统免疫学研究所Georg Gasteiger团队发现，ILC1的效应分化下游是由Hobit在各组织中驱动的。相关论文于2021年8月30日在线发表在《自然—免疫学》杂志上。

通过多路单细胞mRNA测序，研究人员确定了CKit⁺CD127^hiTCF-1^hi早期分化阶段的T-bet⁺先天性淋巴细胞（ILC）。这些细胞存在于不同的器官，并有可能向CD127^intTCF-1^int和CD127^-TCF-1^- ILC1成熟。随着TCF-1的逐渐丧失，分化的ILC1丧失了它们的扩增潜力，同时增加了效应分子的表达，类似于二级淋巴器官中的T细胞分化。转录因子Hobit在TCF-1^hi ILC1中被诱导，是其效应分化所必需的。这些发现揭示了ILC1谱系承诺和效应分化的顺序机制，并且在各组织中是保守的。

这些分析表明，ILC1作为TCF-1^hi细胞出现在外周，并通过局部线索驱动的Hobit依赖性分化途径获得一系列器官特异的效应表型。

据介绍，ILC参与组织的平衡、炎症和抗感染的早期免疫。目前还不清楚ILC是如何获得效应功能的，以及这些机制是否在不同的器官之间有所不同。

附：英文原文

Title: Effector differentiation downstream of lineage commitment in ILC1s is driven by Hobit across tissues

Author: Friedrich, Christin, Taggenbrock, Renske L. R. E., Doucet-Ladevze, Rmi, Golda, Gosia, Moenius, Rebekka, Arampatzi, Panagiota, Kragten, Natasja A. M., Kreymborg, Katharina, Gomez de Agero, Mercedes, Kastenmller, Wolfgang, Saliba, Antoine-Emmanuel, Grn, Dominic, van Gisbergen, Klaas P. J. M., Gasteiger, Georg

Issue&Volume: 2021-08-30

Abstract: Innate lymphoid cells (ILCs) participate in tissue homeostasis, inflammation, and early immunity against infection. It is unclear how ILCs acquire effector function and whether these mechanisms differ between organs. Through multiplexed single-cell mRNA sequencing, we identified cKit+CD127hiTCF-1hi early differentiation stages of T-bet+ ILC1s. These cells were present across different organs and had the potential to mature toward CD127intTCF-1int and CD127TCF-1 ILC1s. Paralleling a gradual loss of TCF-1, differentiating ILC1s forfeited their expansion potential while increasing expression of effector molecules, reminiscent of T cell differentiation in secondary lymphoid organs. The transcription factor Hobit was induced in TCF-1hi ILC1s and was required for their effector differentiation. These findings reveal sequential mechanisms of ILC1 lineage commitment and effector differentiation that are conserved across tissues. Our analyses suggest that ILC1s emerge as TCF-1hi cells in the periphery and acquire a spectrum of organ-specific effector phenotypes through a uniform Hobit-dependent differentiation pathway driven by local cues.

DOI: 10.1038/s41590-021-01013-0

Source: https://www.nature.com/articles/s41590-021-01013-0