Defect of plasmacytoid dendritic cells in warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome patients.
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.
Tassone
Laura
L
Department of Pediatrics, Institute of Molecular Medicine Angelo Nocivelli, Brescia, Italy.
Moratto
Daniele
D
Vermi
William
W
De Francesco
Maria
M
Notarangelo
Lucia D
LD
Porta
Fulvio
F
Lougaris
Vassilios
V
Facchetti
Fabio
F
Plebani
Alessandro
A
Badolato
Raffaele
R
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
C527276:CXCR4 protein, human; D016898:Interferon-alpha; D019718:Receptors, CXCR4