Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Department of Dermatology and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY.
Department of Dermatology and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Dermatology, University Magna Graecia, Catanzaro, Italy.
J Allergy Clin Immunol. 2021 Jul;148(1):148-163. doi: 10.1016/j.jaci.2021.01.001. Epub 2021 Jan 13.
Although atopic dermatitis (AD) often presents in infancy and persists into adulthood, comparative characterization of AD skin among different pediatric age groups is lacking.
We sought to define skin biopsy profiles of lesional and nonlesional AD across different age groups (0-5-year-old infants with disease duration <6 months, 6-11-year-old children, 12-17-year-old adolescents, ≥18-year-old adults) versus age-appropriate controls.
We performed gene expression analyses by RNA-sequencing and real-time PCR (RT-PCR) and protein expression analysis using immunohistochemistry.
T2/T22 skewing, including IL-13, CCL17/thymus and activation-regulated chemokine, IL-22, and S100As, characterized the common AD signature, with a global pathway-level enrichment across all ages. Nevertheless, specific cytokines varied widely. For example, IL-33, IL-1RL1/IL-33R, and IL-9, often associated with early atopic sensitization, showed greatest upregulations in infants. T17 inflammation presented a 2-peak curve, with highest increases in infants (including IL-17A and IL-17F), followed by adults. T1 polarization was uniquely detected in adults, even when compared with adolescents, with significant upregulation in adults of IFN-γ and CXCL9/CXCL10/CXCL11. Although all AD age groups had barrier abnormalities, only adults had significant decreases in filaggrin expression. Despite the short duration of the disease, infant AD presented robust downregulations of multiple barrier-related genes in both lesional and nonlesional skin. Clinical severity scores significantly correlated with T2/T22-related markers in all pediatric age groups.
The shared signature of AD across ages is T2/T22-skewed, yet differential expression of specific T2/T22-related genes, other T pathways, and barrier-related genes portray heterogenetic, age-specific molecular fingerprints.
尽管特应性皮炎（AD）常发生于婴儿期，并持续至成年期，但不同儿科年龄组 AD 皮肤的比较特征尚不清楚。
我们旨在定义不同年龄组（疾病持续时间<6 个月的 0-5 岁婴儿、6-11 岁儿童、12-17 岁青少年、≥18 岁成人）的病变和非病变 AD 与年龄匹配对照之间的皮肤活检特征。
我们通过 RNA 测序和实时 PCR（RT-PCR）进行基因表达分析，并通过免疫组织化学进行蛋白表达分析。
T2/T22 偏倚，包括 IL-13、CCL17/胸腺激活调节趋化因子、IL-22 和 S100A，构成了常见 AD 特征，在所有年龄段均具有全局通路水平的富集。然而，特定的细胞因子差异很大。例如，IL-33、IL-1RL1/IL-33R 和 IL-9，通常与早期特应性致敏有关，在婴儿中表现出最大的上调。T17 炎症呈双峰曲线，婴儿中增加最为明显（包括 IL-17A 和 IL-17F），其次是成人。T1 极化仅在成人中检测到，即使与青少年相比也是如此，成人中 IFN-γ 和 CXCL9/CXCL10/CXCL11 的表达显著上调。尽管所有 AD 年龄组均存在屏障异常，但仅在成人中发现丝聚蛋白表达显著降低。尽管疾病持续时间短，但婴儿 AD 在病变和非病变皮肤中均表现出多个屏障相关基因的强烈下调。临床严重程度评分与所有儿科年龄组的 T2/T22 相关标志物显著相关。
AD 在各年龄段的共同特征是 T2/T22 偏向，但特定 T2/T22 相关基因、其他 T 途径和屏障相关基因的差异表达描绘了异质的、年龄特异性的分子特征。
