Details

Autor(en) / Beteiligte

• Xu, Shasha
• Zhang, Yu
• Liu, Xingjie
• Liu, Huisheng
• Zou, Xinya
• Zhang, Linlin
• Wang, Jing
• Zhang, Zhiwei
• Xu, Xiang
• Li, Mingxia
• Li, Kairui
• Shi, Shuyue
• Zhang, Ying
• Miao, Zhichao
• Zha, Jie
• Yu, Yong

Titel

Nr4a1 marks a distinctive ILC2 activation subset in the mouse inflammatory lung

Ist Teil von

• BMC biology, 2023-10, Vol.21 (1), p.1-218, Article 218

Ort / Verlag

London: BioMed Central Ltd

Erscheinungsjahr

2023

Quelle

SpringerLink

Beschreibungen/Notizen

• Group 2 innate lymphoid cells (ILC2s) are critical sources of type 2 cytokines and represent one of the major tissue-resident lymphoid cells in the mouse lung. However, the molecular mechanisms underlying ILC2 activation under challenges are not fully understood. Here, using single-cell transcriptomics, genetic reporters, and gene knockouts, we identify four ILC2 subsets, including two non-activation subsets and two activation subsets, in the mouse acute inflammatory lung. Of note, a distinct activation subset, marked by the transcription factor Nr4a1, paradoxically expresses both tissue-resident memory T cell (Trm), and effector/central memory T cell (Tem/Tcm) signature genes, as well as higher scores of proliferation, activation, and wound healing, all driven by its particular regulons. Furthermore, we demonstrate that the Nr4a1.sup.+ILC2s are restrained from activating by the programmed cell death protein-1 (PD-1), which negatively modulates their activation-related regulons. PD-1 deficiency places the non-activation ILC2s in a state that is prone to activation, resulting in Nr4a1.sup.+ILC2 differentiation through different activation trajectories. Loss of PD-1 also leads to the expansion of Nr4a1.sup.+ILC2s by the increase of their proliferation ability. The findings show that activated ILC2s are a heterogenous population encompassing distinct subsets that have different propensities, and therefore provide an opportunity to explore PD-1's role in modulating the activity of ILC2s for disease prevention and therapy.