title: CCR2(+)CD103(-) intestinal dendritic cells develop from DC-committed precursors and induce interleukin-17 production by T cells.
abstract: The identification of intestinal macrophages (mφs) and dendritic cells (DCs) is a matter of intense debate. Although CD103(+) mononuclear phagocytes (MPs) appear to be genuine DCs, the nature and origins of CD103(-) MPs remain controversial. We show here that intestinal CD103(-)CD11b(+) MPs can be separated clearly into DCs and mφs based on phenotype, gene profile, and kinetics. CD64(-)CD103(-)CD11b(+) MPs are classical DCs, being derived from Flt3 ligand-dependent, DC-committed precursors, not Ly6C(hi) monocytes. Surprisingly, a significant proportion of these CD103(-)CD11b(+) DCs express CCR2 and there is a selective decrease in CD103(-)CD11b(+) DCs in mice lacking this chemokine receptor. CCR2(+)CD103(-) DCs are present in both the murine and human intestine, drive interleukin (IL)-17a production by T cells in vitro, and show constitutive expression of IL-12/IL-23p40. These data highlight the heterogeneity of intestinal DCs and reveal a bona fide population of CCR2(+) DCs that is involved in priming mucosal T helper type 17 (Th17) responses.
authors.affiliation: 1] Institute of Infection, Immunity and Inflammation, College of Veterinary, Medical and Life Science, University of Glasgow, Glasgow, Scotland, UK [2] VIB Ghent University, Inflammation Research Centre (IRC), Laboratory of Immunoregulation, Ghent (Zwijnaarde), Belgium.
authors.forename: C L
authors.initials: CL
authors.lastname: Scott
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Veterinary, Medical and Life Science, University of Glasgow, Glasgow, Scotland, UK.
authors.forename: C C
authors.initials: CC
authors.lastname: Bain
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Veterinary, Medical and Life Science, University of Glasgow, Glasgow, Scotland, UK.
authors.forename: P B
authors.initials: PB
authors.lastname: Wright
authors.affiliation: VIB Ghent University, Inflammation Research Centre (IRC), Laboratory of Immunoregulation, Ghent (Zwijnaarde), Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Sichien
authors.affiliation: Immunology Section, Lund University, Lund, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Kotarsky
authors.affiliation: Immunology Section, Lund University, Lund, Sweden.
authors.forename: E K
authors.initials: EK
authors.lastname: Persson
authors.affiliation: Immunology Section, Lund University, Lund, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Luda
authors.affiliation: VIB Ghent University, Inflammation Research Centre (IRC), Laboratory of Immunoregulation, Ghent (Zwijnaarde), Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Guilliams
authors.affiliation: VIB Ghent University, Inflammation Research Centre (IRC), Laboratory of Immunoregulation, Ghent (Zwijnaarde), Belgium.
authors.forename: B N
authors.initials: BN
authors.lastname: Lambrecht
authors.affiliation: 1] Immunology Section, Lund University, Lund, Sweden [2] Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: W W
authors.initials: WW
authors.lastname: Agace
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Veterinary, Medical and Life Science, University of Glasgow, Glasgow, Scotland, UK.
authors.forename: S Wf
authors.initials: SW
authors.lastname: Milling
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Veterinary, Medical and Life Science, University of Glasgow, Glasgow, Scotland, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Mowat
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D039001:Integrin alpha Chains / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010586:Phagocytes / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D054390:Receptors, CCR2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*; D000099218:Interferon Regulatory Factor-4
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; D050835:Interferon Regulatory Factors; D018664:Interleukin-12; D020381:Interleukin-17; D054390:Receptors, CCR2; D000099218:Interferon Regulatory Factor-4; C091367:alpha E integrins