Characterization of chemokine receptor expression and cytokine production in circulating CD4+ T cells from patients with atopic dermatitis: up-regulation of C-C chemokine receptor 4 in atopic dermatitis.
BACKGROUND
Th2 and Th1 cells have been suggested to express CCR3/CCR4 and CCR5/CXCR3, respectively.


OBJECTIVE
We examined CCR3, CCR4, CCR5 and CXCR3 expression and cytokine production in peripheral blood CD4+ T cells from patients with atopic dermatitis (AD), which has been postulated to be a Th2-type cell-mediated disease, and then analysed the possible correlation between these values and the levels of several clinical parameters.


METHODS
Intracellular cytokine production and chemokine receptor expression in peripheral blood CD4+ T cells from 40 AD patients and 20 sex- and age-matched healthy control subjects were studied by flow cytometry.


RESULTS
The frequencies of IL-4- and IL-13-producing CD4+ T cells from patients with AD were significantly higher than those from healthy control subjects (IL-4:3.9 +/- 2.1% vs. 1.6 +/- 0.7%, P = 0.0005, IL-13:4.0 +/- 2.1% vs. 1.8 +/- 0.8%, P = 0.0023), whereas the frequencies of IL-2- and IFN-gamma-producing CD4+ T cells were significantly decreased in AD patients (IL-2:38.1 +/- 10.3% vs. 51.3 +/- 6.3%, P = 0.0003, IFN-gamma: 9.9 +/- 3.5% vs. 26.4 +/- 4.6%, P < 0.0001). The percentage of CCR4+ cells in CD4+ CD45RO+ T cells in AD patients was significantly higher than that in healthy control subjects (24.4 +/- 8.0% vs. 10.9 +/- 2.3%, P < 0.0001) and was correlated positively with the total serum IgE, serum lactic dehydrogenase (LDH) level, eosinophil number, eruption score, and IL-4 and IL-13 secretion in CD4+ T cells, and inversely with IL-2 and IFN-gamma secretion in CD4+ T cells. In contrast, CCR3 was not detected on circulating CD4+ T cells even in AD patients. On the other hand, the percentage of CCR5+ or CXCR3+ cells in CD4+ CD45RO+ T cells in AD patients was significantly decreased (CCR5:23.2 +/- 7.0% vs. 28.4 +/- 5.4%, P = 0.023, CXCR3:29.9 +/- 11.4% vs. 38.5 +/- 6.7%, P = 0.028) and was positively correlated with eruption score (P < 0.05). Multiple regression analyses showed that the percentage of CCR4 expression highly correlated with serum IgE, LDH, eosinophil number and eruption in AD patients.


CONCLUSIONS
CCR4+ cells might be involved in the aetiopathogenesis of AD.
Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical School, Tochigi, Japan.
H
H
Okazaki
M
M
Kakurai
D
D
Hirata
H
H
Sato
T
T
Kamimura
N
N
Onai
K
K
Matsushima
H
H
Nakagawa
S
S
Kano
S
S
Minota
D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D016207:Cytokines / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007958:Leukocyte Count; D016015:Logistic Models; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000032:analysis*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
C515354:CCR4 protein, human; D016207:Cytokines; D018793:Interleukin-13; D007376:Interleukin-2; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D007770:L-Lactate Dehydrogenase