title: Alopecia areata profiling shows TH1, TH2, and IL-23 cytokine activation without parallel TH17/TH22 skewing.
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.
authors: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Genetics and Genomics Science, Icahn School of Medicine at Mount Sinai, New York, NY; Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors: Mayte
authors: M
authors: Suárez-Fariñas
authors: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors: Benjamin
authors: B
authors: Ungar
authors: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors: Shinji
authors: S
authors: Noda
authors: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors: Anjali
authors: A
authors: Shroff
authors: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors: Yasaman
authors: Y
authors: Mansouri
authors: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors: Judilyn
authors: J
authors: Fuentes-Duculan
authors: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors: Annette
authors: A
authors: Czernik
authors: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors: Xiuzhong
authors: X
authors: Zheng
authors: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors: Yeriel D
authors: YD
authors: Estrada
authors: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors: Hui
authors: H
authors: Xu
authors: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors: Xiangyu
authors: X
authors: Peng
authors: Department of Dermatology, Tel-Hashomer, Tel Aviv, Israel.
authors: Avner
authors: A
authors: Shemer
authors: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors: James G
authors: JG
authors: Krueger
authors: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors: Mark G
authors: MG
authors: Lebwohl
authors: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Genetics and Genomics Science, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Department of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: Emma.Guttman@mountsinai.org.
authors: Emma
authors: E
authors: Guttman-Yassky
mesh_terms: D000328:Adult; D000506:Alopecia Areata / Q000276:immunology*; D015415:Biomarkers / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology*; D005260:Female; D006801:Humans; D053759:Interleukin-23 / Q000378:metabolism; D053564:Keratins, Hair-Specific / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D011565:Psoriasis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D059467:Transcriptome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018925:Chemokines; D053759:Interleukin-23; D053564:Keratins, Hair-Specific
keywords: Alopecia areata; IL-23; T(H)1; T(H)2; T cell; atopic dermatitis; hair keratin