Monocyte-derived dendritic cells in bipolar disorder.
BACKGROUND
Dendritic cells (DC) are key regulators of the immune system, which is compromised in patients with bipolar disorder. We sought to study monocyte-derived DC in bipolar disorder.


METHODS
Monocytes purified from blood collected from DSM-IV bipolar disorder outpatients (n = 53, 12 without lithium treatment) and healthy individuals (n = 34) were differentiated into DC via standard granulocyte-macrophpage colony-stimulating factor/interleukin-4 culture (with/without 1, 5, and 10 mmol/L lithium chloride). The DC were analyzed for DC-specific and functional markers and for T-cell stimulatory potency.


RESULTS
Monocytes of bipolar patients showed a mild hampering in their differentiation into fully active DC, showing a weak residual expression of the monocyte marker CD14 and a relatively low potency to stimulate autologous T cells. Lithium treatment abolished this mild defect, and monocyte-derived DC of treated bipolar patients showed signs of activation (i.e., an up-regulated potency to stimulate autologous T cells and a higher expression of the DC-specific marker CD1a). This activated phenotype contrasted with the suppressed phenotype of monocyte-derived DC exposed to lithium in vitro (10 mmol/L) during culture.


CONCLUSIONS
Dendritic cells show mild aberrancies in bipolar disorder that are fully restored to even activation after in vivo lithium treatment.
Knijff
Esther M
EM
Department of Immunology, Erasmus Medical Centre, Rotterdam, The Netherlands. e.knijff@erasmusmc.nl
Ruwhof
Cindy
C
de Wit
Harm J
HJ
Kupka
Ralph W
RW
Vonk
Ronald
R
Akkerhuis
Grard W
GW
Nolen
Willem A
WA
Drexhage
Hemmo A
HA
D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis; D018949:Antigens, CD1 / Q000096:biosynthesis; D018692:Antimanic Agents / Q000627:therapeutic use; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology; D001714:Bipolar Disorder / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D015847:Interleukin-4 / Q000502:physiology; D018021:Lithium Chloride / Q000627:therapeutic use; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology; D000097802:CD83 Antigen
D015703:Antigens, CD; D018949:Antigens, CD1; D018692:Antimanic Agents; D001323:Autoantibodies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007136:Immunoglobulins; D015847:Interleukin-4; D018021:Lithium Chloride; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen; C419393:CD1a antigen