Cell-intrinsic role for IFN-α-STAT1 signals in regulating murine Peyer patch plasmacytoid dendritic cells and conditioning an inflammatory response

Blood. 2011 Oct 6;118(14):3879-89. doi: 10.1182/blood-2011-04-349761. Epub 2011 Aug 9.

Abstract

Plasmacytoid dendritic cells (pDCs) reside in bone marrrow and lymphoid organs in homeostatic conditions and typically secrete abundant quantities of type I interferons (IFNs) on Toll-like receptor triggering. Recently, a pDC population was identified within Peyer patches (PPs) of the gut that is distinguished by its lack of IFN production; however, the relationship of PP pDCs to pDCs in other organs has been unclear. We report that PP pDCs are derived from common DC progenitors and accumulate in response to Fms-like tyrosine kinase 3 ligand, yet appear divergent in transcription factor profile and surface marker phenotype, including reduced E2-2 and CCR9 expression. Type I IFN signaling via STAT1 has a cell-autonomous role in accrual of PP pDCs in vivo. Moreover, IFN-α enhances pDC generation from DC progenitors by a STAT1-dependent mechanism. pDCs that have been developed in the presence of IFN-α resemble PP pDCs, produce inflammatory cytokines, stimulate Th17 cell generation, and fail to secrete IFN-α on Toll-like receptor engagement. These results indicate that IFN-α influences the development and function of pDCs by inducing emergence of an inflammatory (Th17-inducing) antigen-presenting subset, and simultaneously regulating accumulation of pDCs in the intestinal microenvironment.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Interferon-alpha / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Peyer's Patches / cytology*
  • STAT1 Transcription Factor / immunology*
  • Stem Cells / cytology
  • Stem Cells / immunology
  • Th17 Cells / cytology
  • Th17 Cells / immunology
  • fms-Like Tyrosine Kinase 3 / immunology

Substances

  • Interferon-alpha
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • fms-Like Tyrosine Kinase 3