title: Expression of the zinc finger transcription factor zDC (Zbtb46, Btbd4) defines the classical dendritic cell lineage.
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.
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Meredith
authors.forename: Kang
authors.initials: K
authors.lastname: Liu
authors.forename: Guillaume
authors.initials: G
authors.lastname: Darrasse-Jeze
authors.forename: Alice O
authors.initials: AO
authors.lastname: Kamphorst
authors.forename: Heidi A
authors.initials: HA
authors.lastname: Schreiber
authors.forename: Pierre
authors.initials: P
authors.lastname: Guermonprez
authors.forename: Juliana
authors.initials: J
authors.lastname: Idoyaga
authors.forename: Cheolho
authors.initials: C
authors.lastname: Cheong
authors.forename: Kai-Hui
authors.initials: KH
authors.lastname: Yao
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Niec
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019070:Cell Lineage / Q000502:physiology*; D003713:Dendritic Cells / Q000378:metabolism / Q000502:physiology*; D004167:Diphtheria Toxin / Q000494:pharmacology; D005786:Gene Expression Regulation; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008545:Melanoma / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D014122:Toxoplasma / Q000472:pathogenicity; D014123:Toxoplasmosis / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D020413:3' Untranslated Regions; D039521:CD11c Antigen; D004167:Diphtheria Toxin; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D014157:Transcription Factors; C574226:Zbtb46 protein, mouse