Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells

Nat Immunol. 2004 Nov;5(11):1124-33. doi: 10.1038/ni1130. Epub 2004 Oct 10.


The fates of dendritic cells (DCs) after antigen presentation have been studied extensively, but the influence of lymphoid microenvironments on DCs is mostly unknown. Here, using splenic stromal cells to mimic the immune microenvironment, we show that contact with stromal cells promoted mature DCs to proliferate in a fibronectin-dependent way and that both stromal cell contact and stromal cell-derived transforming growth factor-beta induced their differentiation into a new regulatory DC subset. We have identified an in vivo counterpart in the spleen with similar phenotype and functions. These differentiated DCs secreted nitric oxide, which mediated the suppression of T cell proliferation in response to antigen presentation by mature DCs. Thus, our findings identify an important mechanism by which the microenvironment regulates immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology*
  • Cell Division / physiology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Genes, Reporter
  • Mice
  • Nitric Oxide / metabolism
  • Spleen / cytology
  • Spleen / immunology*
  • Spleen / metabolism
  • Stromal Cells / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology


  • Nitric Oxide