Compartmental imbalance and aberrant immune function of blood CD123+ (plasmacytoid) and CD11c+ (myeloid) dendritic cells in atopic dermatitis.
Atopic dermatitis (AD) is a pruritic, chronically relapsing skin disease in which Th2 cells play a crucial role in cutaneous and extracutaneous immune reactions. In humans, CD11c+CD123- myeloid dendritic cells (mDC) and CD11c-CD123+ plasmacytoid DC (pDC) orchestrate the decision-making process in innate and acquired immunity. Since the number and function of these blood dendritic cell (DC) subsets reportedly reflect the host immune status, we studied the involvement of the DC subsets in the pathogenesis of AD. Patients with AD had an increased DC number and a low mDC:pDC ratio with pDC outnumbering mDC in the peripheral blood compared with normal subjects and psoriasis patients (a Th1 disease model group). The mDC:pDC ratio was correlated with the total serum IgE level, the ratio of IFN-gamma-producing blood cells:IL-4-producing blood cells, and the disease severity. In vitro allogeneic stimulation of naive CD4+ cells with atopic DC showed that the ability of pDC for Th1 induction was superior or comparable to that of mDC. In skin lesions, pDC infiltration was in close association with blood vessels expressing peripheral neural addressins. Therefore, compartmental imbalance and aberrant immune function of the blood DC subsets may deviate the Th1/Th2 differentiation and thus induce protracted allergic responses in AD.
Hashizume
Hideo
H
Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan. hihashiz@hama-med.ac.jp
Horibe
Takahiro
T
Yagi
Hiroaki
H
Seo
Naohiro
N
Takigawa
Masahiro
M
D000293:Adolescent; D000328:Adult; D000954:Antigens, Surface / Q000096:biosynthesis; D039521:CD11c Antigen / Q000096:biosynthesis* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D002648:Child; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D003876:Dermatitis, Atopic / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D053650:Interleukin-3 Receptor alpha Subunit; D007958:Leukocyte Count; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011565:Psoriasis / Q000097:blood / Q000276:immunology / Q000473:pathology; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000097:blood; D016185:Receptors, Interleukin-3 / Q000096:biosynthesis* / Q000097:blood; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D000954:Antigens, Surface; C515354:CCR4 protein, human; D039521:CD11c Antigen; C515187:CXCR3 protein, human; D016207:Cytokines; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit; C069886:L-selectin counter-receptors; D008565:Membrane Proteins; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D016185:Receptors, Interleukin-3; D007073:Immunoglobulin E