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

Author:

Meredith Matthew M.1,Liu Kang2,Darrasse-Jeze Guillaume3,Kamphorst Alice O.14,Schreiber Heidi A.1,Guermonprez Pierre1,Idoyaga Juliana1,Cheong Cheolho1,Yao Kai-Hui1,Niec Rachel E.5,Nussenzweig Michel C.11

Affiliation:

1. Laboratory of Molecular Immunology, Laboratory of Cellular Physiology and Immunology, and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065

2. Department of Microbiology and Immunology, Columbia University, New York, NY 10027

3. Department of Biotherapy, Institut National de la Santé et de la Recherche Médicale, Faculteì de meìdecine, Universiteì Paris Descartes, Sorbonne Paris Citeì, Paris F-75015, France

4. Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30329

5. Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065

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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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