title: IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis.
abstract: The role of dendritic cells (DCs) in intestinal immune homeostasis remains incompletely defined. Here we show that mice lacking IRF8 transcription-factor-dependent DCs had reduced numbers of T cells in the small intestine (SI), but not large intestine (LI), including an almost complete absence of SI CD8αβ(+) and CD4(+)CD8αα(+) T cells; the latter requiring β8 integrin expression by migratory IRF8 dependent CD103(+)CD11b(-) DCs. SI homing receptor induction was impaired during T cell priming in mesenteric lymph nodes (MLN), which correlated with a reduction in aldehyde dehydrogenase activity by SI-derived MLN DCs, and inefficient T cell localization to the SI. These mice also lacked intestinal T helper 1 (Th1) cells, and failed to support Th1 cell differentiation in MLN and mount Th1 cell responses to Trichuris muris infection. Collectively these results highlight multiple non-redundant roles for IRF8 dependent DCs in the maintenance of intestinal T cell homeostasis.
authors.affiliation: Immunology Section, Lund University, Lund 221 84, Sweden.
authors.forename: Katarzyna M
authors.initials: KM
authors.lastname: Luda
authors.affiliation: Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, 1870 Frederiksberg C, Denmark.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Joeris
authors.affiliation: Immunology Section, Lund University, Lund 221 84, Sweden.
authors.forename: Emma K
authors.initials: EK
authors.lastname: Persson
authors.affiliation: Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, 1870 Frederiksberg C, Denmark.
authors.forename: Aymeric
authors.initials: A
authors.lastname: Rivollier
authors.affiliation: Immunology Section, Lund University, Lund 221 84, Sweden.
authors.forename: Mimoza
authors.initials: M
authors.lastname: Demiri
authors.affiliation: Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, 1870 Frederiksberg C, Denmark.
authors.forename: Katarzyna M
authors.initials: KM
authors.lastname: Sitnik
authors.affiliation: Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, 1870 Frederiksberg C, Denmark.
authors.forename: Lieneke
authors.initials: L
authors.lastname: Pool
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Jacob B
authors.initials: JB
authors.lastname: Holm
authors.affiliation: Manchester Collaborative Centre of Inflammation Research (MCCIR), University of Manchester, Manchester M13 9NT, UK; Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester M13 9PT, UK; Manchester Immunology Group, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Felipe
authors.initials: F
authors.lastname: Melo-Gonzalez
authors.affiliation: Centre for Immune Regulation and Department of Pathology, Oslo University Hospital - Rikshospitalet and University of Oslo, 0027 Oslo, Norway.
authors.forename: Lisa
authors.initials: L
authors.lastname: Richter
authors.affiliation: Inflammation Research Center (IRC), VIB-UGent Department, 9052 Ghent, Belgium.
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.affiliation: Manchester Collaborative Centre of Inflammation Research (MCCIR), University of Manchester, Manchester M13 9NT, UK; Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester M13 9PT, UK; Manchester Immunology Group, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Travis
authors.affiliation: Immunology Section, Lund University, Lund 221 84, Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Svensson-Frej
authors.affiliation: Immunology Section, Lund University, Lund 221 84, Sweden.
authors.forename: Knut
authors.initials: K
authors.lastname: Kotarsky
authors.affiliation: Immunology Section, Lund University, Lund 221 84, Sweden; Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, 1870 Frederiksberg C, Denmark. Electronic address: william.agace@med.lu.se.
authors.forename: William W
authors.initials: WW
authors.lastname: Agace
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018845:CD11 Antigens / Q000235:genetics; D016827:CD8 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology*; D039001:Integrin alpha Chains / Q000235:genetics; D039641:Integrin beta Chains / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D007422:Intestines / Q000166:cytology / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D014258:Trichuris / Q000276:immunology; D000099185:Interferon Regulatory Factor-8; D000099218:Interferon Regulatory Factor-4
chemical_list: D000444:Aldehyde Dehydrogenase; D018845:CD11 Antigens; D016827:CD8 Antigens; D039001:Integrin alpha Chains; D039641:Integrin beta Chains; D050835:Interferon Regulatory Factors; D000099185:Interferon Regulatory Factor-8; D000099218:Interferon Regulatory Factor-4; C409469:CD8 antigen, alpha chain; C433839:CD8alphabeta antigen; C527123:integrin alphaD, mouse; C094865:integrin beta8