Increased endocytic activity in monocyte-derived dendritic cells in patients with psoriasis vulgaris.
OBJECTIVE
The understanding of the pathogenesis of psoriasis vulgaris has focused on T cell mediated immune disorder for many years. Recent studies provide evidence that dendritic cells may be of major importance as regulatory cells driving the psoriasis tissue reaction, and they are one of the therapeutic targets. In order to further characterize the role of dendritic cells in psoriasis, this study was designed to assess the differentiation of dendritic cells from monocytes (MoDC), the expression of phagocytosis related receptors by MoDC, their endocytic activity for fluorescent beads and lucifer yellow as well as their superoxide generation in patients with psoriasis.


METHODS
Twenty eight patients with psoriasis vulgaris and 12 healthy controls were included in the study. MoDC were obtained by culturing monocytes with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 5 days. Cell surface expression of CD1a, CD14, CD40, CD80, CD83, CD86, HLA-DR, mannose receptor (MR) and Fcg receptors by MoDC and their endocytosis of dextran and lucifer yellow were analyzed by flow cytometry. Zymosan ingestion was measured to access the phagocytosis of MoDC.


RESULTS
Differentiation of monocytes to dendritic cells was upregulated in patients manifested as significantly increased expression of CD40, CD80, CD86 and HLA-DR compared with that in healthy controls (P<0.01). Expression of MR and Fcg receptor II (CD32) by MoDC was significantly increased in patients with psoriasis as well (P<0.01). Endocytosis of dextran but not lucifer yellow in patients was significantly higher than controls (P<0.01), and significantly enhanced phagocytosis by increasing zymosan ingestion was also observed (P<0.01) in patients. Taken together, endocytic and phagocytic activity of MoDC in psoriasis was increased than normal persons.


CONCLUSIONS
Enhanced activity of dendritic cells binding and capturing foreign antigens for subsequent antigen presentation and the initiation of immune responses in psoriasis may contribute to the pathogenesis of the disease. The upregulated expression of MR and the enhanced endocytic activity of DC might be an explanation for the absence of skin infection observed in psoriasis.
Department of Dermatology & Venereology, Sir Run Run Shaw Hospital, Medical College, Zhejiang University, Hangzhou 310016, People's Republic of China. zhukejian@mail.hz.zj.cn
Ke-Jian
KJ
Zhu
Hao
H
Cheng
Xiao-Hong
XH
Mao
Li-Min
LM
Lao
Jian-Ping
JP
Cen
Jun
J
Ye
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002681:China; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology*; D004705:Endocytosis / Q000502:physiology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D010587:Phagocytosis / Q000502:physiology; D011565:Psoriasis / Q000276:immunology* / Q000378:metabolism; D011897:Random Allocation; D011956:Receptors, Cell Surface / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology
D015415:Biomarkers; C489017:FCGR1A protein, human; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; D016178:Granulocyte-Macrophage Colony-Stimulating Factor