A single subset of dendritic cells controls the cytokine bias of natural killer T cell responses to diverse glycolipid antigens

Immunity. 2014 Jan 16;40(1):105-16. doi: 10.1016/j.immuni.2013.12.004. Epub 2014 Jan 9.


Many hematopoietic cell types express CD1d and are capable of presenting glycolipid antigens to invariant natural killer T cells (iNKT cells). However, the question of which cells are the principal presenters of glycolipid antigens in vivo remains controversial, and it has been suggested that this might vary depending on the structure of a particular glycolipid antigen. Here we have shown that a single type of cell, the CD8α(+) DEC-205(+) dendritic cell, was mainly responsible for capturing and presenting a variety of different glycolipid antigens, including multiple forms of α-galactosylceramide that stimulate widely divergent cytokine responses. After glycolipid presentation, these dendritic cells rapidly altered their expression of various costimulatory and coinhibitory molecules in a manner that was dependent on the structure of the antigen. These findings show flexibility in the outcome of two-way communication between CD8α(+) dendritic cells and iNKT cells, providing a mechanism for biasing toward either proinflammatory or anti-inflammatory responses.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens / immunology
  • Antigens, CD / metabolism
  • Antigens, CD1d / metabolism
  • CD8 Antigens / metabolism
  • Cell Communication
  • Cytokines / metabolism*
  • Dendritic Cells / immunology*
  • Galactosylceramides / immunology
  • Gene Expression Regulation / immunology
  • Homeostasis
  • Inflammation / immunology
  • Lectins, C-Type / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Minor Histocompatibility Antigens
  • Natural Killer T-Cells / immunology*
  • Receptors, Cell Surface / metabolism


  • Antigens
  • Antigens, CD
  • Antigens, CD1d
  • CD8 Antigens
  • CD8alpha antigen
  • Cytokines
  • DEC-205 receptor
  • Galactosylceramides
  • Lectins, C-Type
  • Minor Histocompatibility Antigens
  • Receptors, Cell Surface
  • alpha-galactosylceramide