title: Cutting Edge: Plasmacytoid Dendritic Cells in Late-Stage Lupus Mice Defective in Producing IFN-α.
abstract: Plasmacytoid dendritic cells (pDCs) are professional type I IFN producers believed to promote lupus. However, questions exist about whether they function at the same level throughout the course of lupus disease. We analyzed high-purity pDCs sorted from lupus mice. Although pDCs produced a large amount of IFN-α during disease initiation, those sorted from late-stage lupus mice were found to be defective in producing IFN-α. These pDCs expressed an increased level of MHC, suggesting a functional drift to Ag presentation. We examined the potential mechanism behind the defect and identified a novel transcriptional factor, Foxj2, which repressed the expression of several genes in pDCs, but not IFN-α. Dysregulation in pDCs appears to be predisposed, because they exhibited an altered transcriptional profile before the onset of clinical signs. Our results suggest that pDCs do not function the same throughout the disease course and lose the ability to produce IFN-α in late-stage lupus mice.
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061;
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Liao
authors.affiliation: Department of Crop and Soil Environmental Sciences, College of Agriculture and Life Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061;
authors.forename: Song
authors.identifier: http://orcid.org/0000-0002-8133-3944
authors.initials: S
authors.lastname: Li
authors.affiliation: Virginia Bioinformatics Institute, Blacksburg, VA 24061;
authors.forename: Robert E
authors.initials: RE
authors.lastname: Settlage
authors.affiliation: Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697;
authors.forename: Sha
authors.identifier: http://orcid.org/0000-0002-0044-6403
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061;
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061;
authors.forename: Alec M
authors.initials: AM
authors.lastname: Reihl
authors.affiliation: Department of Civil and Environmental Engineering, College of Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061; and.
authors.forename: Husen
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Virginia Bioinformatics Institute, Blacksburg, VA 24061;
authors.forename: Saikumar V
authors.initials: SV
authors.lastname: Karyala
authors.affiliation: Edward Via College of Osteopathic Medicine, Blacksburg, VA 24060.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Reilly
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061;
authors.forename: S Ansar
authors.initials: SA
authors.lastname: Ahmed
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061; xinluo@vt.edu.
authors.forename: Xin M
authors.initials: XM
authors.lastname: Luo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D051858:Forkhead Transcription Factors; C485809:Foxj2 protein, mouse; D016898:Interferon-alpha; D034741:RNA, Small Interfering