title: Intestinal CD103(+)CD11b(-) dendritic cells restrain colitis via IFN-γ-induced anti-inflammatory response in epithelial cells.
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.
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
authors.forename: A R B M
authors.initials: AR
authors.lastname: Muzaki
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
authors.forename: P
authors.initials: P
authors.lastname: Tetlak
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
authors.forename: J
authors.initials: J
authors.lastname: Sheng
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
authors.forename: S C
authors.initials: SC
authors.lastname: Loh
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
authors.forename: Y A
authors.initials: YA
authors.lastname: Setiagani
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore.
authors.forename: M
authors.initials: M
authors.lastname: Poidinger
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore.
authors.forename: F
authors.initials: F
authors.lastname: Zolezzi
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
authors.forename: K
authors.initials: K
authors.lastname: Karjalainen
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
authors.forename: C
authors.initials: C
authors.lastname: Ruedl
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology*; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D016264:Dextran Sulfate; D060467:Disease Resistance / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D066257:Heparin-binding EGF-like Growth Factor / Q000235:genetics / Q000276:immunology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000276:immunology; D039001:Integrin alpha Chains / Q000235:genetics / Q000276:immunology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction
chemical_list: D015703:Antigens, CD; D039481:CD11b Antigen; C529914:Clec9a protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; C583637:IDO1 protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D039001:Integrin alpha Chains; D036341:Intercellular Signaling Peptides and Proteins; D019409:Interleukin-15; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; C091367:alpha E integrins; C118370:interleukin-18 binding protein; D018664:Interleukin-12; D007371:Interferon-gamma; D016264:Dextran Sulfate