Alopecia areata profiling shows TH1, TH2, and IL-23 cytokine activation without parallel TH17/TH22 skewing - 06/11/15
Abstract |
Background |
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 TH1/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 TH1/interferon markers (IFNG and CXCL10/CXCL9) were those noted in TH2 (IL13, CCL18, CCL26, thymic stromal lymphopoietin, and periostin), TH9/IL-9, IL-23 (p40 and p19), and IL-16 mediators (all P < .05). There were no increases in TH17/TH22 markers. Hair keratin (KRT) expressions (ie, KRT86 and KRT85) were significantly suppressed in lesional skin. Greater scalp involvement (>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 TH2, TH1, IL-23, and IL-9/TH9 cytokine activation, suggesting consideration of anti-TH2, anti-TH1, and anti–IL-23 targeting strategies. Similar to psoriasis and AD, clinical trials with selective antagonists are required to dissect key pathogenic pathways.
Le texte complet de cet article est disponible en PDF.Key words : Alopecia areata, T cell, TH1, TH2, IL-23, hair keratin, atopic dermatitis
Abbreviations used : AA, AD, AT, AU, DC, DEG, FCH, HI, ITGAX, JAK, KRT, KRTAP, MI, PDE4, POSTN, STAT1, TSLP
Plan
| B.U., J.G.K., M.S.-F., and S.N. were supported by grant no. 5UL1RR024143-02 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and the NIH Roadmap for Medical Research. E.G.-Y was supported by the Dermatology Foundation Physician Scientist Career Development Award. |
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| Disclosure of potential conflict of interest: J. G. Krueger has received research support and personal fees from Novartis, Pfizer, Janssen, Lilly, Merck, Kadmon, Dermira, Boehringer, BMS, and Paraxel; has received research support from Amgen, Innovaderm, and Kyowa; and has received research support and personal fees from Serono, BiogenIdec, Delenex, AbbVie, Sanofi, Baxter, Xenoport, and Kineta. M. G. Lebwohl has received research support from AbGenomics, AbbVie, Amgen, Anacor, Aqua, Canfite Biopharma, Celgene, Clinuvel, Coronado Biosciences, Ferndale, Lilly, Janssen Biotech, LEO Pharma, Merz, Novartis, Pfizer, Sandoz, and Valeant. E. Guttman-Yassky is a board member for Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, MedImmune, Celgene, Anacor, and LEO Pharma; has received consultancy fees from Regeneron, Sanofi Aventis, MedImmune, Celgene, Stiefel/GlaxoSmithKline, Celsus, BMS, Amgen, and Drais; and has received research support from Regeneron, Celgene, BMS, and Janssen. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 136 - N° 5
P. 1277-1287 - novembre 2015 Retour au numéro
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