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Nat Immunol. 2014 Jan;15(1):98-108. doi: 10.1038/ni.2768. Epub 2013 Dec 1.

Comparative transcriptional and functional profiling defines conserved programs of intestinal DC differentiation in humans and mice.

Author information

1
1] Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California, USA. [2] The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA. [3].
2
1] Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California, USA. [2] The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA.
3
Department of Microbiology and Immunology, Sandler Asthma Basic Research Center, University of California San Francisco, San Francisco, California, USA.
4
Department of Surgery, Stanford University School of Medicine, Stanford, California, USA.
5
Center for Autoimmune and Musculoskeletal Diseases, the Feinstein Institute for Medical Research, Manhasset, New York, USA.
6
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
7
1] The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA. [2] Palo Alto Institute for Research & Education, Palo Alto, California, USA.
8
1] Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California, USA. [2] The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA. [3] Palo Alto Institute for Research & Education, Palo Alto, California, USA.

Abstract

Dendritic cells (DCs) that orchestrate mucosal immunity have been studied in mice. Here we characterized human gut DC populations and defined their relationship to previously studied human and mouse DCs. CD103(+)Sirpα(-) DCs were related to human blood CD141(+) DCs and to mouse intestinal CD103(+)CD11b(-) DCs and expressed markers of cross-presenting DCs. CD103(+)Sirpα(+) DCs aligned with human blood CD1c(+) DCs and mouse intestinal CD103(+)CD11b(+) DCs and supported the induction of regulatory T cells. Both CD103(+) DC subsets induced the TH17 subset of helper T cells, while CD103(-)Sirpα(+) DCs induced the TH1 subset of helper T cells. Comparative analysis of transcriptomes revealed conserved transcriptional programs among CD103(+) DC subsets and identified a selective role for the transcriptional repressors Bcl-6 and Blimp-1 in the specification of CD103(+)CD11b(-) DCs and intestinal CD103(+)CD11b(+) DCs, respectively. Our results highlight evolutionarily conserved and divergent programming of intestinal DCs.

PMID:
24292363
PMCID:
PMC3942165
DOI:
10.1038/ni.2768
[Indexed for MEDLINE]
Free PMC Article

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