Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)(+) TH2/TH1 cell imbalance, whereas adults acquire CLA(+) TH22/TC22 cell subsets.
Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)(+) TH2/TH1 cell imbalance, whereas adults acquire CLA(+) TH22/TC22 cell subsets.
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DOI：
10.1016/j.jaci.2015.05.049
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发表时间：
2015-10
期刊：
影响因子：
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通讯作者：
Guttman-Yassky E
中科院分区：
文献类型：
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作者：
Czarnowicki T;Esaki H;Gonzalez J;Malajian D;Shemer A;Noda S;Talasila S;Berry A;Gray J;Becker L;Estrada Y;Xu H;Zheng X;Suárez-Fariñas M;Krueger JG;Paller AS;Guttman-Yassky E
识别儿童与成人特应性皮炎（AD）中CLA+极化T细胞亚群之间的差异和相似性对于指导针对儿童的新治疗至关重要。比较早期儿童AD、成人AD和对照组中皮肤归巢（CLA+）与全身（CLA−）“极性”CD 4和CD 8 T细胞亚群的活化标志物和频率。流式细胞术用于测量记忆亚群中的CD 69/ICOS/HLA-DR频率以及IFN-γ、IL-13、IL-9、IL-17和IL-22细胞因子，分别定义CD 4和CD 8细胞中的Th 1/Tc 1、Th 2/Tc 2、Th 9/Tc 9、Th 17/Tc 17和Th 22/Tc 22群体。我们比较了19名5岁以下儿童和42名具有良好特征的中度至重度AD的成人以及年龄匹配的对照组（17名儿童和25名成人）的外周血。在儿童中观察到选择性ICOS激活（P<0.001）。与对照组相比，AD儿童和成人的CLA+ Th 2 T细胞均显著扩增，但AD儿童的CLA+ Th 1 T细胞下降幅度更大（17% vs. 7.4%，P=0.007）。与成人不同，在儿童AD CLA− T细胞中没有检测到失衡，CLA+或CLA−隔室中的Th 22 T细胞频率也没有改变。在皮肤归巢人群中，AD成人产生IL-22的CD 4和CD 8 T细胞的频率增加（分别为9.5%和4.5%; 8.6%和2.4%; P<0.001），HLA-DR活化增加（P<0.01）。这些数据表明，皮肤归巢T细胞内的Th 2激活可能会导致儿童AD，而Th 1 T细胞的反调节减少可能会导致Th 2过度激活。AD的Th 22“传播”在幼儿中未见，可能受免疫发育、疾病慢性化或复发性皮肤感染的影响。治疗儿童AD的治疗方法可能最好是纠正Th 2/Th 1失衡，而成人也可能受益于IL-22靶向治疗。虽然儿童AD的特征是Th 1/Th 2失调，但成人AD伴有较高的慢性激活和Th 22/Tc 22组分。
Identifying differences and similarities between CLA+ polarized T-cell subsets in pediatric vs. adult atopic dermatitis (AD) is critical for directing new treatments towards children. To compare activation markers and frequencies of skin-homing (CLA+) vs. systemic (CLA−) “polar” CD4 and CD8 T-cell subsets in early pediatric AD, adult AD and controls. Flow cytometry was used to measure CD69/ICOS/HLA-DR frequency in memory subsets as well as IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines, defining Th1/Tc1, Th2/Tc2, Th9/Tc9, Th17/Tc17, and Th22/Tc22 populations in CD4 and CD8 cells, respectively. We compared peripheral blood from 19 children <5 years and 42 adults with well-characterized moderate to severe AD, as well as age-matched controls (17 children and 25 adults). Selective ICOS activation (P<0.001) was seen in children. CLA+ Th2 T-cells were markedly expanded in both AD children and adults compared to controls, but decreases in CLA+ Th1 T-cells were greater in AD children (17% vs. 7.4%, P=0.007). Unlike in adults, no imbalances were detected in pediatric AD CLA− T-cells, nor were there altered frequencies of Th22 T-cells within CLA+ or CLA− compartments. Adults with AD had increased frequency of IL-22-producing CD4 and CD8 T-cells within the skin-homing population (9.5% vs. 4.5%; 8.6% vs. 2.4%, respectively; P<0.001) as well as increased HLA-DR activation (P<0.01). These data suggest that Th2 activation within skin-homing T-cells may drive AD in children and that reduced counter-regulation by Th1 T-cells may contribute to excess Th2 activation. Th22 “spreading” of AD is not seen in young children and may be influenced by immune development, disease chronicity or recurrent skin infections. Therapeutic approaches to treat AD in children may be best directed to correction of Th2/Th1 imbalance, while adults might also benefit from IL-22 targeted therapies. While AD in children is characterized by Th1/Th2 dysregulation, AD in adults is accompanied by higher chronic activation and a Th22/Tc22 component.