Deciphering the transcriptional network of the dendritic cell lineage

Jennifer C. Miller, Brian D. Brown, Tal Shay, Emmanuel L. Gautier, Vladimir Jojic, Ariella Cohain, Gaurav Pandey, Marylene Leboeuf, Kutlu G. Elpek, Julie Helft, Daigo Hashimoto, Andrew Chow, Jeremy Price, Melanie Greter, Milena Bogunovic, Angelique Bellemare-Pelletier, Paul S. Frenette, Gwendalyn J. Randolph, Shannon J. Turley, Miriam MeradClaudia Jakubzick, Adam J. Best, Jamie Knell, Ananda Goldrath, Daphne Koller, Nadia Cohen, Patrick Brennan, Michael Brenner, Aviv Regev, Anne Fletcher, Deepali Malhotra, Radu Jianu, David Laidlaw, Jim Collins, Kavitha Narayan, Katelyn Sylvia, Joonsoo Kang, Roi Gazit, Derrick J. Rossi, Francis Kim, Tata Nageswara Rao, Amy Wagers, Susan A. Shinton, Richard R. Hardy, Paul Monach, Natalie A. Bezman, Joseph C. Sun, Charlie C. Kim, Lewis L. Lanier, Tracy Heng

Research output: Contribution to journalArticlepeer-review

482 Scopus citations

Abstract

Although much progress has been made in the understanding of the ontogeny and function of dendritic cells (DCs), the transcriptional regulation of the lineage commitment and functional specialization of DCs in vivo remains poorly understood. We made a comprehensive comparative analysis of CD8 +, CD103 +, CD11b + and plasmacytoid DC subsets, as well as macrophage DC precursors and common DC precursors, across the entire immune system. Here we characterized candidate transcriptional activators involved in the commitment of myeloid progenitor cells to the DC lineage and predicted regulators of DC functional diversity in tissues. We identified a molecular signature that distinguished tissue DCs from macrophages. We also identified a transcriptional program expressed specifically during the steady-state migration of tissue DCs to the draining lymph nodes that may control tolerance to self tissue antigens.

Original languageEnglish (US)
Pages (from-to)888-899
Number of pages12
JournalNature immunology
Volume13
Issue number9
DOIs
StatePublished - Sep 2012

Bibliographical note

Funding Information:
We thank colleagues of the ImmGen Project, especially the technical team, including M. Painter, J. Ericson and S. Davis, for contributions; C. Benoist for contributions to the design and writing of the manuscript; and eBioscience and Affymetrix for support of the ImmGen Project. Supported by the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (R24 AI072073 to the ImmGen Project (led by C. Benoist); AI080884 and HL086899 to M.M.; JDRF172010770 and DP2DK083052-01 to B.D.B.; DK074500 and AI045757 to S.J.T.; HL69438, DK056638, HL097819 and HL097700 to P.S.F.; and U54CA149145 to V.J.).

Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.

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