title: IRF4 transcription-factor-dependent CD103(+)CD11b(+) dendritic cells drive mucosal T helper 17 cell differentiation.
abstract: CD103(+)CD11b(+) dendritic cells (DCs) represent the major migratory DC population within the small intestinal lamina propria (SI-LP), but their in vivo function remains unclear. Here we demonstrate that intestinal CD103(+)CD11b(+) DC survival was dependent on interferon regulatory factor 4 (IRF4). Mice with a DC deletion in Irf4 displayed reduced numbers of intestinal interleukin 17 (IL-17)-secreting helper T 17 (Th17) cells and failed to support Th17 cell differentiation in draining mesenteric lymph nodes (MLN) following immunization. The latter was associated with a selective reduction in CD103(+)CD11b(+) MLN DCs and DC derived IL-6. Immunized Il6(-/-) mice failed to support Th17 cell differentiation in MLN in vivo and CD103(+)CD11b(+) MLN DCs supported IL-6-dependent Th17 cell differentiation in vitro. Together, our results suggest a central role for IRF4-dependent, IL-6 producing CD103(+)CD11b(+) DCs in intestinal Th17 cell differentiation.
authors.affiliation: Immunology Section, Lund University, Lund 221 84, Sweden.
authors.forename: Emma K
authors.initials: EK
authors.lastname: Persson
authors.forename: Heli
authors.initials: H
authors.lastname: Uronen-Hansson
authors.forename: Monika
authors.initials: M
authors.lastname: Semmrich
authors.forename: Aymeric
authors.initials: A
authors.lastname: Rivollier
authors.forename: Karin
authors.initials: K
authors.lastname: Hägerbrand
authors.forename: Jan
authors.initials: J
authors.lastname: Marsal
authors.forename: Sigurdur
authors.initials: S
authors.lastname: Gudjonsson
authors.forename: Ulf
authors.initials: U
authors.lastname: Håkansson
authors.forename: Boris
authors.initials: B
authors.lastname: Reizis
authors.forename: Knut
authors.initials: K
authors.lastname: Kotarsky
authors.forename: William W
authors.initials: WW
authors.lastname: Agace
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017384:Sequence Deletion; D058504:Th17 Cells / Q000276:immunology* / Q000502:physiology*; D000099218:Interferon Regulatory Factor-4
chemical_list: D015703:Antigens, CD; D039481:CD11b Antigen; D039001:Integrin alpha Chains; D050835:Interferon Regulatory Factors; D020381:Interleukin-17; D000099218:Interferon Regulatory Factor-4; C091367:alpha E integrins