Decreased GATA3 levels cause changed mouse cutaneous innate lymphoid cell fate, facilitating hair follicle recycling,Developmental Cell

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Decreased GATA3 levels cause changed mouse cutaneous innate lymphoid cell fate, facilitating hair follicle recycling
Developmental Cell ( IF 10.7 ) Pub Date : 2024-05-08 , DOI: 10.1016/j.devcel.2024.04.015
Guanqun Ren ₁ , Yime Zhang ₁ , Jiamin Liu ₁ , Wenwen Cheng ₂ , Di Wu ₃ , Mengwei Han ₁ , Yanyu Zeng ₁ , Xingyu Zhao ₁ , Luni Hu ₁ , Min Zeng ₁ , Rama Krishna Gurram ₄ , Xiaole Hu ₂ , Bo Zhou ₂ , Zhiyuan Hou ₅ , Jinfang Zhu ₄ , Wenfei Jin ₆ , Chao Zhong ₇

Affiliation

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.
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; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China; Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20892, USA.
Institute of Systems Biomedicine, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing 100191, China.
CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
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.

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.

中文翻译：

GATA3水平降低导致小鼠皮肤先天淋巴细胞命运改变，促进毛囊回收

在小鼠中，皮肤驻留的 2 型先天淋巴细胞 (ILC2) 表现出一些类似 ILC3 的特征。然而，潜在的机制仍然难以捉摸。在这里，我们观察到与典型的 ILC2 相比，ILC2 主调节因子 GATA3 在皮肤 ILC2 (cILC2) 中的表达较低，这与其在 cILC2 转录控制中的功能不同作用相符。 GATA3 水平的降低使得 RORγt 命运映射 (RORγt) cILC2 在出生后几天得以扩展，与 ILC3 表现出一定的相似性。单细胞轨迹分析显示 RORγt 和 GATA3 依次促进 RORγt cILC2 差异。值得注意的是，在毛囊回收过程中，这些 RORγt cILC2 在毛囊真皮乳头 (DP) 区域周围积累，以促进该过程。从机制上讲，我们发现 RORγt cILC2 上的 GATA3 介导的整合素 α3β1 上调是它们在 DP 周围定位所必需的。总体而言，我们的研究证明了 GATA3 在 cILC2 中具有独特的调节作用，特别是在促进 RORγt cILC2 的分化以促进毛囊回收方面。

更新日期：2024-05-08

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