Metaphocytes are IL-22BP-producing cells regulated by ETS transcription factor Spic and essential for zebrafish barrier immunity
Changlong Zhao,
Yunbo Li,
Jinlin Tang,
Qiuxia Zhou,
Xi Lin,
Zilong Wen
Affiliations
Changlong Zhao
Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China
Yunbo Li
Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China
Jinlin Tang
Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China
Qiuxia Zhou
Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China
Xi Lin
Brigham and Women’s Hospital, Harvard Medical School, Boston, MS 02115, USA
Zilong Wen
Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China; Greater Bay Biomedical Innocenter, Shenzhen Bay Laboratory, Shenzhen 518055, China; Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University−Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 518036, China; Department of Immunology and Microbiology, School of Life Science, Southern University of Science and Technology, Shenzhen 518055, China; Corresponding author
Summary: Metaphocytes are tissue-resident macrophage (TRM)/dendritic cell (DC)-like cells of non-hematopoietic origin in zebrafish barrier tissues. One remarkable property of metaphocytes is their ability to capture soluble antigens from the external environment via transepithelial protrusions, a unique function manifested by specialized subpopulations of the TRMs/DCs in mammal barrier tissues. Yet, how metaphocytes acquire myeloid-like cell properties from non-hematopoietic precursors and how they regulate barrier immunity remains unknown. Here, we show that metaphocytes are in situ generated from local progenitors guided by the ETS transcription factor Spic, the deficiency of which results in the absence of metaphocytes. We further document that metaphocytes are the major IL-22BP-producing cells, and the depletion of metaphocytes causes dysregulated barrier immunity that resembles the phenotype of IL-22BP-deficient mice. These findings reveal the ontogeny, development, and function of metaphocytes in zebrafish, which facilitates our understanding of the nature and function of the mammalian TRM/DC counterparts.
