title: Cell-intrinsic role for IFN-α-STAT1 signals in regulating murine Peyer patch plasmacytoid dendritic cells and conditioning an inflammatory response.
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.
authors.affiliation: Department of Immunology and Center for Inflammation and Cancer, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Haiyan S
authors.initials: HS
authors.lastname: Li
authors.forename: Alexander
authors.initials: A
authors.lastname: Gelbard
authors.forename: Gustavo J
authors.initials: GJ
authors.lastname: Martinez
authors.forename: Eiji
authors.initials: E
authors.lastname: Esashi
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Zhang
authors.forename: Hoainam
authors.initials: H
authors.lastname: Nguyen-Jackson
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Willem W
authors.initials: WW
authors.lastname: Overwijk
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Watowich
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D016898:Interferon-alpha / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010581:Peyer's Patches / Q000166:cytology*; D050794:STAT1 Transcription Factor / Q000276:immunology*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology; D051941:fms-Like Tyrosine Kinase 3 / Q000276:immunology
chemical_list: D016898:Interferon-alpha; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D051941:fms-Like Tyrosine Kinase 3