Abstract
A crosstalk between commensals, gut immune cells, and colonic epithelia is required for a proper function of intestinal mucosal barrier. Here we investigated the importance of two distinct intestinal dendritic cell (DC) subsets in controlling intestinal inflammation. We show that Clec9A-diphtheria toxin receptor (DTR) mice after depletion of CD103(+)CD11b(-) DCs developed severe, low-dose dextran sodium sulfate (DSS)-induced colitis, whereas the lack of CD103(+)CD11b(+) DCs in Clec4a4-DTR mice did not exacerbate intestinal inflammation. The CD103(+)CD11b(-) DC subset has gained a functional specialization that able them to repress inflammation via several epithelial interferon-γ (IFN-γ)-induced proteins. Among others, we identified that epithelial IDO1 and interleukin-18-binding protein (IL-18bp) were strongly modulated by CD103(+)CD11b(-) DCs. Through its preferential property to express IL-12 and IL-15, this particular DC subset can induce lymphocytes in colonic lamina propria and in epithelia to secrete IFN-γ that then can trigger a reversible early anti-inflammatory response in intestinal epithelial cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / genetics
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Antigens, CD / immunology*
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CD11b Antigen / genetics
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CD11b Antigen / immunology*
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Colitis / chemically induced
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Colitis / genetics
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Colitis / immunology*
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Colitis / pathology
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Colon / immunology
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Colon / pathology
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Dendritic Cells / immunology*
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Dendritic Cells / pathology
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Dextran Sulfate
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Disease Resistance / immunology*
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Epithelial Cells / immunology
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Epithelial Cells / pathology
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Female
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Gene Expression Regulation
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Heparin-binding EGF-like Growth Factor / genetics
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Heparin-binding EGF-like Growth Factor / immunology
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Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics
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Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology
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Integrin alpha Chains / genetics
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Integrin alpha Chains / immunology*
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / immunology
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Interferon-gamma / genetics
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Interferon-gamma / immunology*
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Interleukin-12 / genetics
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Interleukin-12 / immunology
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Interleukin-15 / genetics
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Interleukin-15 / immunology
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Intestinal Mucosa / immunology
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Intestinal Mucosa / pathology
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Lectins, C-Type / genetics
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Lectins, C-Type / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Receptors, Immunologic / genetics
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Receptors, Immunologic / immunology
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Signal Transduction
Substances
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Antigens, CD
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CD11b Antigen
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Clec9a protein, mouse
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Heparin-binding EGF-like Growth Factor
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IDO1 protein, mouse
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Indoleamine-Pyrrole 2,3,-Dioxygenase
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Integrin alpha Chains
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Intercellular Signaling Peptides and Proteins
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Interleukin-15
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Lectins, C-Type
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Receptors, Immunologic
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alpha E integrins
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interleukin-18 binding protein
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Interleukin-12
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Interferon-gamma
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Dextran Sulfate