PLZF restricts intestinal ILC3 function in gut defense

Yaru Xu; Huasheng Zhang; Shuai Wu; Jianyue Liu; Hongzhi Liu; Dongdi Wang; Youqin Zhang; Hongshen Niu; Xiaohui Su; Jiping Sun; Lei Shen

doi:10.1038/s41423-023-00975-5

PLZF restricts intestinal ILC3 function in gut defense

Cell Mol Immunol. 2023 Apr;20(4):379-388. doi: 10.1038/s41423-023-00975-5. Epub 2023 Jan 25.

Authors

Yaru Xu^#¹, Huasheng Zhang^#¹, Shuai Wu¹, Jianyue Liu¹, Hongzhi Liu¹, Dongdi Wang¹, Youqin Zhang¹, Hongshen Niu¹, Xiaohui Su^{1

2}, Jiping Sun^{3

4}, Lei Shen^{5

6

7}

Affiliations

¹ Shanghai Institute of Immunology, Department of Immunology and Microbiology, and Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
² Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
³ Shanghai Institute of Immunology, Department of Immunology and Microbiology, and Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. sunjiping@shsmu.edu.cn.
⁴ Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. sunjiping@shsmu.edu.cn.
⁵ Shanghai Institute of Immunology, Department of Immunology and Microbiology, and Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. lshen@shsmu.edu.cn.
⁶ Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. lshen@shsmu.edu.cn.
⁷ Department of Neurosurgery, Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China. lshen@shsmu.edu.cn.

^# Contributed equally.

Abstract

Group 3 innate lymphoid cells (ILC3s) play important roles in maintaining intestinal homeostasis by protecting the host from pathogen infections and tissue inflammation. The transcription factor PLZF (promyelocytic leukemia zinc finger), encoded by zinc finger BTB domain containing 16 (Zbtb16), is highly and transiently expressed in ILC precursors (ILCPs). However, the role of PLZF in regulating ILC3 development and function remains unknown. Here, we show that PLZF was specifically expressed in mature intestinal ILC3s compared with other ILC subsets. PLZF was dispensable for ILC3 development. However, PLZF deficiency in ILC3s resulted in increased innate interleukin-22 (IL-22) secretion and protection against gut infection and inflammation. Mechanistically, PLZF negatively regulated IL-22 expression by ILC3s in a cell-intrinsic manner by binding to the IL-22 promoter region for transcriptional repression. Together, our data suggest that PLZF restricts intestinal ILC3 function to regulate gut immune homeostasis.

Keywords: Biological sciences; Immunology; Innate immune cells; Innate lymphoid cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Gene Expression
Humans
Immunity, Innate*
Inflammation / metabolism
Lymphocytes*
Promyelocytic Leukemia Zinc Finger Protein* / metabolism
Transcription Factors / metabolism

Substances

Transcription Factors
Promyelocytic Leukemia Zinc Finger Protein