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

Guanqun Ren; Yime Zhang; Jiamin Liu; Wenwen Cheng; Di Wu; Mengwei Han; Yanyu Zeng; Xingyu Zhao; Luni Hu; Min Zeng; Rama Krishna Gurram; Xiaole Hu; Bo Zhou; Zhiyuan Hou; Jinfang Zhu; Wenfei Jin; Chao Zhong

doi:10.1016/j.devcel.2024.04.015

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

Dev Cell. 2024 May 5:S1534-5807(24)00268-5. doi: 10.1016/j.devcel.2024.04.015. Online ahead of print.

Authors

Guanqun Ren¹, Yime Zhang¹, Jiamin Liu¹, Wenwen Cheng², Di Wu³, Mengwei Han¹, Yanyu Zeng¹, Xingyu Zhao¹, Luni Hu¹, Min Zeng¹, Rama Krishna Gurram⁴, Xiaole Hu², Bo Zhou², Zhiyuan Hou⁵, Jinfang Zhu⁴, Wenfei Jin⁶, Chao Zhong⁷

Affiliations

¹ 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.
² Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
³ 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.
⁴ 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.
⁵ Institute of Systems Biomedicine, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing 100191, China.
⁶ CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China. Electronic address: jinwf@sustech.edu.cn.
⁷ 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. Electronic address: zhongc@pku.edu.cn.

PMID: 38723629
DOI: 10.1016/j.devcel.2024.04.015

Abstract

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^fm+) cILC2s after postnatal days, displaying certain similarities to ILC3s. Single-cell trajectory analysis showed a sequential promotion of the RORγt^fm+ cILC2 divergency by RORγt and GATA3. Notably, during hair follicle recycling, these RORγt^fm+ 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^fm+ 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^fm+ cILC2s to facilitate hair follicle recycling.

Keywords: GATA3; RORγt; cutaneous ILC2; hair follicle recycling; integrin α3β1.