Impact of human myelin on the maturation and function of human monocyte-derived dendritic cells.
Macrophages and dendritic cells (DC) play an important role in the immunopathology of multiple sclerosis. We analyzed the impact of human myelin on monocyte-derived DC and describe their immunostimulatory capacity. Cells were grown on myelin and stimulated with LPS or a defined maturation cocktail. DC activation was analyzed by the expression of cell surface markers and the secretion of cytokines and chemokines. The immunostimulatory capacity of DC was assessed by allogeneic mixed-leukocyte reactions via proliferation. Additionally, their ability to bias T cells towards Th1, Th17 or Treg differentiation was investigated. We found that phagocytosis of myelin impaired the activation of DC, displayed by an impaired ability to stimulate allogeneic T cells, an increased production of TGF-beta1 and a diminished upregulation of CCR7 but did not affect the differentiation into T helper cell subsets. We hypothesize that myelin influences DC activation and plays a pivotal role in balancing immunity and tolerance.
Gredler
Viktoria
V
Clinical Department of Neurology, Innsbruck Medical University, Austria.
Ebner
Susanne
S
Schanda
Kathrin
K
Forstner
Markus
M
Berger
Thomas
T
Romani
Nikolaus
N
Reindl
Markus
M
D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D009103:Multiple Sclerosis / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D054400:Receptors, CCR7 / Q000096:biosynthesis / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology
D015703:Antigens, CD; C515370:CCR7 protein, human; D016207:Cytokines; D008070:Lipopolysaccharides; D054400:Receptors, CCR7