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

  1. Haiyan S. Li1,
  2. Alexander Gelbard24,
  3. Gustavo J. Martinez1,5,
  4. Eiji Esashi1,
  5. Huiyuan Zhang1,
  6. Hoainam Nguyen-Jackson1,5,
  7. Yong-Jun Liu1,5,
  8. Willem W. Overwijk2,5, and
  9. Stephanie S. Watowich1,5
  1. Departments of 1Immunology and Center for Inflammation and Cancer,
  2. 2Melanoma Medical Oncology, and
  3. 3Head & Neck Surgery, University of Texas M. D. Anderson Cancer Center, Houston, TX;
  4. 4Bobby R. Alford Department of Otolaryngology, Head & Neck Surgery, Baylor College of Medicine, Houston, TX; and
  5. 5Graduate School of Biomedical Sciences, Houston, TX


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.

  • Submitted April 19, 2011.
  • Accepted July 27, 2011.
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