Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Medicine Innovation Center for Fundamental Researches on Major Immunology-Related Diseases, Peking University, Beijing 100191, China; Institute of Systems Biomedicine, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing 100191, China.
Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
Dev Cell. 2024 Jul 22;59(14):1809-1823.e6. doi: 10.1016/j.devcel.2024.04.015. Epub 2024 May 8.
In mice, skin-resident type 2 innate lymphoid cells (ILC2s) exhibit some ILC3-like characteristics. However, the underlying mechanism remains elusive. Here, we observed lower expression of the ILC2 master regulator GATA3 specifically in cutaneous ILC2s (cILC2s) compared with canonical ILC2s, in line with its functionally divergent role in transcriptional control in cILC2s. Decreased levels of GATA3 enabled the expansion of RORγt fate-mapped (RORγt) cILC2s after postnatal days, displaying certain similarities to ILC3s. Single-cell trajectory analysis showed a sequential promotion of the RORγt cILC2 divergency by RORγt and GATA3. Notably, during hair follicle recycling, these RORγt cILC2s accumulated around the hair follicle dermal papilla (DP) region to facilitate the process. Mechanistically, we found that GATA3-mediated integrin α3β1 upregulation on RORγt cILC2s was required for their positioning around the DP. Overall, our study demonstrates a distinct regulatory role of GATA3 in cILC2s, particularly in promoting the divergence of RORγt cILC2s to facilitate hair follicle recycling.
在小鼠中，皮肤驻留型 2 型先天淋巴细胞（ILC2）表现出一些 ILC3 样特征。然而，其潜在机制仍不清楚。在这里，我们观察到皮肤 ILC2（cILC2）中 ILC2 主调控因子 GATA3 的表达明显低于经典 ILC2，这与其在 cILC2 中转录控制的功能分化作用一致。GATA3 水平降低使 RORγt 命运映射（RORγt）cILC2 在出生后几天内得以扩增，表现出与 ILC3 的某些相似之处。单细胞轨迹分析显示 RORγt 和 GATA3 依次促进 RORγt cILC2 的分化。值得注意的是，在毛囊循环过程中，这些 RORγt cILC2 在毛囊真皮乳头（DP）区域周围积累，以促进这一过程。从机制上讲，我们发现 RORγt cILC2 上 GATA3 介导的整合素 α3β1 上调对于它们在 DP 周围的定位是必需的。总的来说，我们的研究表明 GATA3 在 cILC2 中具有独特的调节作用，特别是在促进 RORγt cILC2 的分化以促进毛囊循环方面。
