Transcription factor TCF-1 regulates the functions, but not the development, of lymphoid tissue inducer subsets in different tissues
Mingzhu Zheng,
Chen Yao,
Gang Ren,
Kairui Mao,
Hyunwoo Chung,
Xi Chen,
Gangqing Hu,
Lei Wang,
Xuemei Luan,
Difeng Fang,
Dan Li,
Chao Zhong,
Xiaoxiao Lu,
Nikki Cannon,
Mingxu Zhang,
Avinash Bhandoola,
Keji Zhao,
John J. O’Shea,
Jinfang Zhu
Affiliations
Mingzhu Zheng
Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Microbiology and Immunology School of Medicine, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Southeast University, Nanjing, Jiangsu 210009, China; Corresponding author
Chen Yao
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Immunology & Kidney Cancer Program, Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Gang Ren
Laboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA; College of Animal Science and Technology, Northwest A&F University, Shannxi 712100, China
Kairui Mao
Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China
Hyunwoo Chung
Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Xi Chen
Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Gangqing Hu
Laboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA; Bioinformatics Core, West Virginia University, Morgantown, WV 26506, USA; Department of Microbiology, Immunology, and Cell Biology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA
Lei Wang
Bioinformatics Core, West Virginia University, Morgantown, WV 26506, USA
Xuemei Luan
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China
Difeng Fang
Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Dan Li
Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Department of Clinical Laboratory, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China
Chao Zhong
Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
Xiaoxiao Lu
Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Nikki Cannon
Bioinformatics Core, West Virginia University, Morgantown, WV 26506, USA
Mingxu Zhang
Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Haining 314400, China
Avinash Bhandoola
Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Keji Zhao
Laboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
John J. O’Shea
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Jinfang Zhu
Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding author
Summary: Lymphoid tissue inducer (LTi) cells, a subset of innate lymphoid cells (ILCs), play an essential role in the formation of secondary lymphoid tissues. However, the regulation of the development and functions of this ILC subset is still elusive. In this study, we report that the transcription factor T cell factor 1 (TCF-1), just as GATA3, is indispensable for the development of non-LTi ILC subsets. While LTi cells are still present in TCF-1-deficient mice, the organogenesis of Peyer’s patches (PPs), but not of lymph nodes, is impaired in these mice. LTi cells from different tissues have distinct gene expression patterns, and TCF-1 regulates the expression of lymphotoxin specifically in PP LTi cells. Mechanistically, TCF-1 may directly and/or indirectly regulate Lta, including through promoting the expression of GATA3. Thus, the TCF-1-GATA3 axis, which plays an important role during T cell development, also critically regulates the development of non-LTi cells and tissue-specific functions of LTi cells.
