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PLZF restricts intestinal ILC3 function in gut defense

Cellular & Molecular Immunology volume 20, pages 379–388 (2023)Cite this article

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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.

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Acknowledgements

We thank Dr. Xingxu Huang from Shanghai Tech University for the PLZF-deficient mice and Dr. Xiaohuan Guo from Tsinghua University for the Rag2−/−Il2rg−/− mice. We thank all the members from the Shen laboratory for their help and suggestions. We thank the Flow Cytometry Core in Shanghai Institute of Immunology and Animal Facility at Shanghai Jiao Tong University School of Medicine for service and assistance.

Funding

This study was supported by grant 2020YFA0509200 (to LS) from the Ministry of Science and Technology of China, grant 81971487 (to LS) from the National Natural Science Foundation of China, grants 20ZR1430200 and 20142202300 (to LS) from the Science and Technology Commission of Shanghai Municipality, grant 20194Y0275 (to JS) from the Shanghai Municipal Health Commission, and the Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases.

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  1. These authors contributed equally: Yaru Xu, Huasheng Zhang.

Authors and 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

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

  2. Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Xiaohui Su, Jiping Sun & Lei Shen

  3. 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

    Lei Shen

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  1. Yaru Xu
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Contributions

YX, HZ, and SW performed the experiments and analyzed the data. JL, HL, DW, YZ, HN and XS performed flow cytometry and in vitro experiments. JS and LS wrote the manuscript and conceived, designed, and supervised the project.

Corresponding authors

Correspondence to Jiping Sun or Lei Shen.

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The authors declare no competing interests.

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Xu, Y., Zhang, H., Wu, S. et al. PLZF restricts intestinal ILC3 function in gut defense. Cell Mol Immunol 20, 379–388 (2023). https://doi.org/10.1038/s41423-023-00975-5

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