Inflammatory Th1 and Th17 in the Intestine Are Each Driven by Functionally Specialized Dendritic Cells with Distinct Requirements for MyD88

Cell Rep. 2016 Oct 25;17(5):1330-1343. doi: 10.1016/j.celrep.2016.09.091.


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.

Keywords: A20; MyD88; Th1; Th17; dendritic cells; inflammation; small intestine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / metabolism
  • Antigens, CD / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Gastrointestinal Microbiome
  • Gene Expression Regulation
  • Humans
  • Inflammation / pathology*
  • Interleukin-17 / metabolism
  • Intestinal Mucosa
  • Intestines / pathology*
  • Mice
  • Mice, Transgenic
  • Myeloid Differentiation Factor 88 / metabolism*
  • Phenotype
  • Th1 Cells / immunology*
  • Th17 Cells / immunology*


  • Antigens, CD
  • Cytokines
  • Interleukin-17
  • Myeloid Differentiation Factor 88