title: Inflammatory Th1 and Th17 in the Intestine Are Each Driven by Functionally Specialized Dendritic Cells with Distinct Requirements for MyD88.
abstract: Normal dynamics between microbiota and dendritic cells (DCs) support modest numbers of T cells, yet these do not cause inflammation. The DCs that induce inflammatory T cells and the signals that drive this process remain unclear. Here, we demonstrate that small intestine DCs lacking the signaling attenuator A20 induce inflammatory T cells and that the signals perceived and antigen-presenting cell (APC) functions are unique for different DC subsets. Thus, although CD103+CD11b-DCs exclusively instruct IFNγ+T cells, CD103+CD11b+DCs exclusively instruct IL-17+T cells. Surprisingly, APC functions of both DC subsets are upregulated in a MyD88-independent fashion. In contrast, CD103-CD11b+DCs instruct both IFNγ+and IL-17+T cells, and only the IL-17-inducing APC functions require MyD88. In disease pathogenesis, both CD103-CD11b+and CD103+CD11b+DCs expand pathologic Th17 cells. Thus, in disease pathogenesis, specific DCs instruct specific inflammatory T cells.
authors: Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
authors: Jie
authors: J
authors: Liang
authors: Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
authors: Hsin-I
authors: HI
authors: Huang
authors: Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Physics, Universidade Estadual Paulista, São José do Rio Preto, SP 15054-000, Brazil.
authors: Fernanda P
authors: FP
authors: Benzatti
authors: Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
authors: Amelia B
authors: AB
authors: Karlsson
authors: Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
authors: Junyi J
authors: JJ
authors: Zhang
authors: Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Biology, Universität Erlangen-Nürnberg, Erlangen 91058, Germany.
authors: Nourhan
authors: N
authors: Youssef
authors: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Averil
authors: A
authors: Ma
authors: Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.
authors: Laura P
authors: LP
authors: Hale
authors: Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: gianna.hammer@duke.edu.
authors: Gianna E
authors: GE
authors: Hammer
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D000069196:Gastrointestinal Microbiome; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D020381:Interleukin-17 / Q000378:metabolism; D007413:Intestinal Mucosa; D007422:Intestines / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D010641:Phenotype; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D020381:Interleukin-17; D053594:Myeloid Differentiation Factor 88
keywords: A20; MyD88; Th1; Th17; dendritic cells; inflammation; small intestine