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

Allergy Asthma Proc. 2015 Nov-Dec;36(6):e140-5. doi: 10.2500/aap.2015.36.3901.

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

MeSH terms

  • Adolescent
  • Adult
  • Antigens, Surface / metabolism
  • Biomarkers
  • Cytokines / blood
  • Cytokines / metabolism
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / metabolism*
  • Dermatitis, Atopic / pathology
  • Female
  • Flow Cytometry
  • Gene Expression
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Immunophenotyping
  • Male
  • Monocytes / immunology
  • Monocytes / metabolism*
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*
  • Young Adult

Substances

  • Antigens, Surface
  • Biomarkers
  • Cytokines
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Immunoglobulin E