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.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Antigens, CD / immunology
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Antigens, CD / metabolism
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Antigens, CD1 / immunology
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Antigens, CD1 / metabolism
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CD11b Antigen / immunology
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CD11b Antigen / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Cells, Cultured
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Cluster Analysis
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Cross-Priming / genetics
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Cross-Priming / immunology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Flow Cytometry
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Glycoproteins / immunology
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Glycoproteins / metabolism
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Humans
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Integrin alpha Chains / immunology
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Integrin alpha Chains / metabolism
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Integrins / genetics
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Integrins / immunology
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Intestinal Mucosa / immunology*
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Mice
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Mice, Knockout
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Mice, Transgenic
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Microscopy, Confocal
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Oligonucleotide Array Sequence Analysis
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Receptors, Chemokine / genetics
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Receptors, Chemokine / immunology
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism
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Th17 Cells / immunology
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Th17 Cells / metabolism
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Transcriptome / genetics
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Transcriptome / immunology*
Substances
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Antigens, CD
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Antigens, CD1
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CD11b Antigen
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CD1C protein, human
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Glycoproteins
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Integrin alpha Chains
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Integrins
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Receptors, Chemokine
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alpha E integrins