The maturation-dependent production of interleukin-16 is impaired in monocyte-derived dendritic cells from atopic dermatitis patients but is restored by inflammatory cytokines TNF-alpha and IL-1beta.
BACKGROUND
Maturation of dendritic cells (DCs) influences important DC functions such as production of cytokines. Recently, DCs were identified as a source of interleukin-16 (IL-16), a chemotactic factor for DCs themselves, CD4+ T cells, and eosinophils. There is evidence that DC-derived IL-16 may contribute to the pathogenesis of atopic dermatitis (AD).


OBJECTIVE
To investigate the production of IL-16 during differentiation of monocytes into DCs in healthy individuals and patients with AD.


METHODS
IL-16 production was investigated by quantitative real-time RT-PCR, intracellular cytokine staining, immunoblotting, and ELISA.


RESULTS
DCs generated from peripheral monocytes by 5-day culture in the presence of IL-4 and granulocyte/macrophage colony-stimulating factor acquired the capability to synthesize, store, and secrete IL-16. Storage and release of IL-16 was further enhanced during final DC maturation induced by additional 3-day culture with tumor necrosis factor-alpha (TNF-alpha) and monocyte-conditioned medium. Maturation, as determined by up-regulation of CD83 and CD86 surface expression, and production of IL-16, but not production of IL-10 and IL-12p40 was impaired in day 8 DCs derived from AD patients compared to those from healthy donors. Stimulation of day 8 DCs from AD patients with TNF-alpha and IL-1beta enhanced the expression of CD83 and CD86 and restored the production of IL-16.


CONCLUSIONS
Signals involved in the activation and maturation of DCs enhance their capacity to produce IL-16. Functional abnormalities present in patients with AD at the monocyte level may account for impaired maturation and IL-16 production of monocyte-derived DCs.
Reich
Kristian
K
Department of Dermatology, Georg-August-University, Göttingen, Germany. kreich@gwdg.de
Hugo
Sabine
S
Middel
Peter
P
Blaschke
Volker
V
Heine
Andrea
A
Neumann
Christine
C
D015703:Antigens, CD / Q000096:biosynthesis; D051940:B7-2 Antigen; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002469:Cell Separation; D002633:Chemotaxis; D016207:Cytokines / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007150:Immunohistochemistry; D007249:Inflammation; D007375:Interleukin-1 / Q000378:metabolism*; D019410:Interleukin-16 / Q000096:biosynthesis* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009000:Monocytes / Q000378:metabolism*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation; D000097802:CD83 Antigen
D015703:Antigens, CD; D051940:B7-2 Antigen; D016207:Cytokines; D018076:DNA, Complementary; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007136:Immunoglobulins; D007375:Interleukin-1; D019410:Interleukin-16; D008562:Membrane Glycoproteins; D012313:RNA; D014409:Tumor Necrosis Factor-alpha; D000097802:CD83 Antigen; C497964:CD86 protein, human