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Transcriptome analysis reveals intrinsic pro-inflammatory signaling in healthy African American skin

Published:October 28, 2021DOI:https://doi.org/10.1016/j.jid.2021.09.031

      ABSTRACT

      Differences in morphology and physiology of darkly pigmented compared to lightly pigmented skin are well recognized. There are also disparities in prevalence and clinical features for many inflammatory skin diseases including atopic dermatitis and psoriasis; however, the underlying mechanisms are largely unknown. We compared the baseline gene expression in full thickness skin biopsies from healthy individuals self-reporting as African American (AA) or White Non-Hispanic (WNH). Extensively validated RNA-Seq analysis identified 570 differentially expressed genes (DEG) in AA skin including immunoglobulins and their receptors such as FCER1G; pro-inflammatory genes such as TNFα, IL-32; EDC (epidermal differentiation cluster) and keratin genes. DEGs were functionally enriched for inflammatory responses, keratinization, cornified envelope formation. RNA-seq analysis of 3D human skin equivalents (HSE) made from AA and WNH primary keratinocytes revealed 360 DEGs (some shared with skin) which were enriched by similar functions. AA HSE appeared more responsive to TNFα pro-inflammatory effects. Finally, AA-specific DEGs in skin and HSE significantly overlapped with molecular signatures of skin in AD and psoriasis patients. Overall, these findings suggest the existence of intrinsic pro-inflammatory circuits in AA keratinocytes/skin that may account for disease disparities and will help to build a foundation for the development of targeted skin disease prevention.

      Keywords

      Abbreviations:

      AA (African American), AD (atopic dermatitis), DEG (differentially expressed gene), EMT (epithelial-mesenchymal transition), FLG (filaggrin), FC (fold change), GSEA (gene set enrichment analysis), HSE (3D human skin equivalent), Ig (immunoglobulin), LCE (late cornified envelope), LOR (loricrin), NHEK (normal human epidermal keratinocytes), qRT-PCR (quantitative real-time reverse-transcription polymerase chain reaction), RNA-seq (RNA sequencing), TF (transcription factor), TNFα (tumor necrosis factor alpha), WNH (White Non-Hispanic)
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