Expression of TLR2 and TLR4 on peripheral blood monocytes during exacerbation of atopic dermatitis

Abstract

In atopic dermatitis (AD), monocytes, which accumulate in the inflamed skin, are characterized by a significantly impaired Toll-like receptors (TLR) expression and TLR2-mediated cytokine secretion. However, data on expression of TLR on monocytes of peripheral blood (PB) in AD are not available. To investigate TLR2 and TLR4 expression on PB monocytes during AD exacerbation and to assess the relationships between TLR expressions with AD clinical severity and with serum interleukin (IL) 4, IL-10, and IL-17a levels. The objective Scoring Atopic Dermatitis index, TLR2 and TLR4 expression on CD14(+) human leukocyte antigen-DR (HLA-DR(+)) PB monocytes by flow cytometry, serum IL-4, IL-10, IL-17a (enzyme-linked immunosorbent assay) and total immunoglobulin E levels were measured at study entry and after 4 months in patients with AD and healthy controls. Eighty-two patients with AD, 35 women (45.1%) and 47 men (54.9%), mean (standard deviation [SD]) age, 42.2 ± 11.5 years, were included. Thirty healthy volunteers served as controls. We observed a significant difference in the levels of TLR2 expression in the CD14(+) HLA-DR(+) PB monocytes of patients with AD (mean [SD], 51.6 ± 23.1% and 264 ± 118 cells/mm(3)) at exacerbation (but not at the end of the 4-month postexacerbation period) compared with the healthy control subjects (mean [SD], 22.3 ± 10.6% and 105 ± 50 cells/mm(3); p < 0.001). TLR4 expression in PB monocytes was significantly greater in AD (mean [SD], 50.1 ± 20.9% and 275 ± 114 cells/mm(3)) than in the healthy subjects (mean [SD], 31.2 ± 8.7% and 147 ± 41 cells/mm(3); p < 0.001) both at exacerbation and at the 4-month postexacerbation period. Significant correlations between TLR2(+) (but not TLR4(+)) PB monocytes and the objective Scoring Atopic Dermatitis index (r = 0.604, p < 0.001), serum levels of IL-17a and TLR2(+) PB monocytes (r = 0.416, p = 0.027), and IL-4 and TLR2(+) PB monocytes (r = -0.307, p = 0.014) were observed during AD exacerbation. PB CD14(+) HLA-DR(+) TLR2(+) monocytes might have a role in the skewing of a T-helper 2/T-helper 17-mediated immune response during AD flare.