Expression of the zinc finger transcription factor zDC (Zbtb46, Btbd4) defines the classical dendritic cell lineage

• Type of Material: Article
• Authors: Matthew M. Meredith, Laboratory of Molecular Immunology; Kang Liu, Columbia University; Guillaume Darrasse-Jeze, Universiteì Paris Descartes; Alice Silva, Emory University; Heidi A. Schreiber, Laboratory of Molecular Immunology; Pierre Guermonprez, Laboratory of Molecular Immunology; Juliana Idoyaga, Laboratory of Cellular Physiology and Immunology; Cheolho Cheong, Laboratory of Cellular Physiology and Immunology; Kai-Hui Yao, Laboratory of Molecular Immunology; Rachel E. Niec, Memorial Sloan-Kettering Cancer Center; Michel C. Nussenzweig, The Rockefeller University
• Language: English
• Date: 2012-06-04
• Publisher: Rockefeller University Press
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Meredith et al.
• License: Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1084/jem.20112675
• Title of Journal or Parent Work: The Journal of Experimental Medicine
• Volume: 209
• Issue: 6
• Start Page: 1153
• End Page: 1165
• Grant/Funding Information: This work was supported in part by National Institutes of Health (NIH) grant number AI051573.; M.M. Meredith was supported by an NIH Immunity and Infectious Disease Training Grant. K. Liu was supported by Dana Neuroimmunology grant and a Pilot Grant funded by P30 AR044535/AR/NIAMS/NIH Columbia University Medical Center Skin Disease Research Center.
• Research Categories: Biology, Microbiology; Health Sciences, Immunology

Abstract

Classical dendritic cells (cDCs), monocytes, and plasmacytoid DCs (pDCs) arise from a common bone marrow precursor (macrophage and DC progenitors [MDPs]) and express many of the same surface markers, including CD11c. We describe a previously uncharacterized zinc finger transcription factor, zDC (Zbtb46, Btbd4), which is specifically expressed by cDCs and committed cDC precursors but not by monocytes, pDCs, or other immune cell populations. We inserted diphtheria toxin (DT) receptor (DTR) cDNA into the 3′ UTR of the zDC locus to serve as an indicator of zDC expression and as a means to specifically deplete cDCs. Mice bearing this knockin express DTR in cDCs but not other immune cell populations, and DT injection into zDC-DTR bone marrow chimeras results in cDC depletion. In contrast to previously characterized CD11c-DTR mice, non-cDCs, including pDCs, monocytes, macrophages, and NK cells, were spared after DT injection in zDC-DTR mice. We compared immune responses to Toxoplasma gondii and MO4 melanoma in DT-treated zDC- and CD11c-DTR mice and found that immunity was only partially impaired in zDC-DTR mice. Our results indicate that CD11c-expressing non-cDCs make significant contributions to initiating immunity to parasites and tumors.