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

Li HS, Gelbard A, Martinez GJ, Esashi E, Zhang H, Nguyen-Jackson H, Liu YJ, Overwijk WW, Watowich SS
Blood. 2011 118 (14): 3879-89

PMID: 21828128 · PMCID: PMC3193265 · DOI:10.1182/blood-2011-04-349761

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.

MeSH Terms (11)

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

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