title: Defect of plasmacytoid dendritic cells in warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome patients.
abstract: Warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome is a genetic disease that is caused by heterozygous mutations of the CXCR4 gene. These mutations confer an increased leukocyte response to the CXCR4-ligand CXCL12, resulting in abnormal homeostasis of many leukocyte types, including neutrophils and lymphocytes. Analysis of the myeloid and plasmacytoid dendritic cell blood counts in WHIM patients revealed a striking defect in the number of plasmacytoid dendritic cells as well as a partial reduction of the number of myeloid dendritic cells, compared with healthy subjects. Moreover, the production of interferon-α by mononuclear cells in response to herpes simplex infection, or after stimulation with the Toll-like receptor 9 ligand CpG, was undetectable in WHIM patients. Because plasmacytoid dendritic cells play a key role in the defense against viruses and their generation and motility are in part dependent on CXCR4, we hypothesized that the susceptibility of WHIM patients to warts is related to the abnormal homeostasis of plasmacytoid dendritic cells.
authors.affiliation: Department of Pediatrics, Institute of Molecular Medicine Angelo Nocivelli, Brescia, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Tassone
authors.forename: Daniele
authors.initials: D
authors.lastname: Moratto
authors.forename: William
authors.initials: W
authors.lastname: Vermi
authors.forename: Maria
authors.initials: M
authors.lastname: De Francesco
authors.forename: Lucia D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: Fulvio
authors.initials: F
authors.lastname: Porta
authors.forename: Vassilios
authors.initials: V
authors.lastname: Lougaris
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchetti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.forename: Raffaele
authors.initials: R
authors.lastname: Badolato
mesh_terms: D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000096:biosynthesis*; D009154:Mutation; D000081207:Primary Immunodeficiency Diseases; D019718:Receptors, CXCR4 / Q000235:genetics; D014860:Warts / Q000235:genetics / Q000276:immunology / Q000473:pathology
chemical_list: C527276:CXCR4 protein, human; D016898:Interferon-alpha; D019718:Receptors, CXCR4