特应性皮炎加重期外周血单核细胞上TLR2和TLR4的表达
Expression of TLR2 and TLR4 on peripheral blood monocytes during exacerbation of atopic dermatitis.
作者信息
Tsybikov Namjil N, Petrisheva Irina, Fefelova Elena V, Kuznik Boris I, Magen Eli
机构信息
Pathophysiology Department, Chita Medical Academy, Chita, Russia.
出版信息
Allergy Asthma Proc. 2015 Nov-Dec;36(6):e140-5. doi: 10.2500/aap.2015.36.3901.
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.
背景
在特应性皮炎（AD）中，积聚在炎症皮肤中的单核细胞具有Toll样受体（TLR）表达显著受损以及TLR2介导的细胞因子分泌受损的特征。然而，关于AD患者外周血（PB）单核细胞上TLR表达的数据尚不可得。
目的
研究AD病情加重期间PB单核细胞上TLR2和TLR4的表达，并评估TLR表达与AD临床严重程度以及与血清白细胞介素（IL）-4、IL-10和IL-17a水平之间的关系。
方法
在研究开始时及4个月后，对AD患者和健康对照者测量客观特应性皮炎评分指数、通过流式细胞术检测CD14(+)人类白细胞抗原-DR（HLA-DR(+)）PB单核细胞上的TLR2和TLR4表达、血清IL-4、IL-10、IL-17a（酶联免疫吸附测定）以及总免疫球蛋白E水平。
结果
纳入了82例AD患者，其中35例女性（45.1%），47例男性（54.9%），平均（标准差[SD]）年龄为42.2±11.5岁。30名健康志愿者作为对照。我们观察到，与健康对照者（平均[SD]，22.3±10.6%和105±50个细胞/mm³）相比，AD患者在病情加重时（但在病情加重后4个月时未观察到）CD14(+) HLA-DR(+) PB单核细胞中TLR2表达水平存在显著差异（平均[SD]，51.6±23.1%和264±118个细胞/mm³；p<0.001）。在病情加重时以及病情加重后4个月时，AD患者PB单核细胞中TLR4表达均显著高于健康受试者（平均[SD]，50.1±20.9%和275±114个细胞/mm³；p<0.001）。在AD病情加重期间，观察到TLR2(+)（而非TLR4(+)）PB单核细胞与客观特应性皮炎评分指数（r = 0.604，p<0.001）、血清IL-17a水平与TLR2(+) PB单核细胞（r = 0.416，p = 0.027）以及IL-4与TLR2(+) PB单核细胞（r = -0.307，p = 0.014）之间存在显著相关性。
结论
PB CD14(+) HLA-DR(+) TLR2(+)单核细胞可能在AD发作期间辅助性T细胞2/辅助性T细胞17介导的免疫反应失衡中发挥作用。
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