Interferon-alpha differentially affects homeostasis of human plasmacytoid and myeloid dendritic cells.
Interferon-alpha (IFN-alpha) is widely used for the treatment of malignant and viral diseases. Conflicting results of IFN-alpha-mediated effects on dendritic cell (DC) homeostasis have been reported and its impact on human blood DC is largely unknown. We investigated the phenotypic, migratory, and allostimulatory activities of plasmacytoid DCs (PDCs) and myeloid DCs (MDCs) upon in vitro exposure to IFN-alpha without the addition of exogenous DC growth factors. IFN-alpha-exposed PDCs exhibited an increase in viability but showed an immature phenotype and a diminished allostimulatory potential. Furthermore, IFN-alpha-treated PDCs displayed a dramatically augmented expression of CD54 and CD62L as well as an increased migratory response to CC chemokine ligand (CCL)19, CXC chemokine ligand (CXCL)11, and CXCL12, suggesting an enhanced ability to migrate into peripheral lymph nodes through high endothelial venules. Myeloid DCs exposed to IFN-alpha exhibited a matured phenotype with an increased propensity to migrate toward lymph node chemokines, yet without gaining an enhanced allostimulatory capacity. Our results provide new insights into the differential immunomodulatory action of IFN-alpha on distinct human blood DC subsets and thus, may present translational significance.
Cicinnati
Vito R
VR
Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Germany.
Kang
Jinyu
J
Hou
Jing
J
Lindemann
Monika
M
Koop
Karsten
K
Tüting
Thomas
T
Gerken
Guido
G
Beckebaum
Susanne
S
D000704:Analysis of Variance; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000494:pharmacology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D007155:Immunologic Factors; D016898:Interferon-alpha; D019707:Receptors, Chemokine