Alopecia areata profiling shows T_H1, T_H2, and IL-23 cytokine activation without parallel T_H17/T_H22 skewing

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• 作者：Mayte Suá ; rez-Fariñ ; as ; PhD^a ; ^b ; ^c ; ^d ; ^e ; ^&lowast ; ; Benjamin Ungar ; BA^a ; ^e ; ^&lowast ; ; Shinji Noda ; MD ; PhD^e ; ^&lowast ; ; Anjali Shroff ; MD^a ; Yasaman Mansouri ; MD^a ; Judilyn Fuentes-Duculan ; MD^e ; Annette Czernik ; MD^a ; Xiuzhong Zheng ; MSc^e ; Yeriel D. Estrada ; MSc^a ; Hui Xu ; MSc^a ; Xiangyu Peng ; MSc^a ; Avner Shemer ; MD^g ; James G. Krueger ; MD ; PhD^e ; Mark G. Lebwohl ; MD^a ; Emma Guttman-Yassky ; MD ; PhD^a ; ^c ; ^e ; ^f ; ^{Emma.Guttman@mountsinai.org" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Alopecia areata ; T cell ; TH1 ; TH2 ; IL-23 ; hair keratin ; atopic dermatitis
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：136
• 期：5
• 页码：1277-1287
• 全文大小：3359 K

文摘

Alopecia areata (AA) is a common T cell–mediated disorder with limited therapeutics. A molecular profile of cytokine pathways in AA tissues is lacking. Although studies have focused on T_H1/IFN-γ responses, several observations support a shared genetic background between AA and atopy.

Objective

We sought to define the AA scalp transcriptome and associated biomarkers with comparisons with atopic dermatitis (AD) and psoriasis.

Methods

We performed microarray and RT-PCR profiling of 27 lesional and 17 nonlesional scalp samples from patients with AA for comparison with normal scalp samples (n = 6). AA gene expression was also compared with samples from patients with lesional or nonlesional AD and those with psoriasis. A fold change of greater than 1.5 and a false discovery rate of less than 0.05 were used for differentially expressed genes (DEGs).

Results

We established the AA transcriptomes (lesional vs nonlesional: 734 DEGs [297 upregulated and 437 downregulated]; lesional vs normal: 4230 DEGs [1980 upregulated and 2250 downregulated]), including many upregulated immune and downregulated hair keratin genes. Equally impressive as upregulation in T_H1/interferon markers (IFNG and CXCL10/CXCL9) were those noted in T_H2 (IL13, CCL18, CCL26, thymic stromal lymphopoietin, and periostin), T_H9/IL-9, IL-23 (p40 and p19), and IL-16 mediators (all P < .05). There were no increases in T_H17/T_H22 markers. Hair keratin (KRT) expressions (ie, KRT86 and KRT85) were significantly suppressed in lesional skin. Greater scalp involvement (&gt;25%) was associated with greater immune and keratin dysregulation and larger abnormalities in nonlesional scalp samples (ie, CXCL10 and KRT85).

Conclusions

Our data associate the AA signature with T_H2, T_H1, IL-23, and IL-9/T_H9 cytokine activation, suggesting consideration of anti-T_H2, anti-T_H1, and anti–IL-23 targeting strategies. Similar to psoriasis and AD, clinical trials with selective antagonists are required to dissect key pathogenic pathways.