TY - JOUR
T1 - Transcriptome Analysis Reveals Intrinsic Proinflammatory Signaling in Healthy African American Skin
AU - Klopot, Anna
AU - Baida, Gleb
AU - Kel, Alexander
AU - Tsoi, Lam C.
AU - Perez White, Bethany E.
AU - Budunova, Irina
N1 - Funding Information:
We acknowledge Northwestern University Genomics Facility/Sequencing Core and Northwestern University Skin Biology & Diseases Resource-based Center (P30AR075049) Skin Tissue Engineering and Morphology Core for technical support. We also acknowledge RNA-sequencing analysis in human skin equivalent by LC Sciences (Houston, TX). This work was supported in part by R01GM112945 and 1R01AI125366 (to IB), K01AR072773 (to BEPW), NIH K01AR072129 (to LCT), the Dermatology Foundation, the National Psoriasis Foundation, and the Arthritis National Research Foundation (to LCT). Conceptualization: IB; Formal Analysis: AKe, LCT; Funding Acquisition: IB; BEPW, LCT; Investigation: AKl, GB, BEPW; Methodology: IB, BEPW; Validation: AKl; Visualization: AKl, GB, BEPW; Writing - Original Draft Preparation: IB; Writing - Review and Editing: IB, AKl, BEPW
Funding Information:
We acknowledge Northwestern University Genomics Facility/Sequencing Core and Northwestern University Skin Biology & Diseases Resource-based Center (P30AR075049) Skin Tissue Engineering and Morphology Core for technical support. We also acknowledge RNA-sequencing analysis in human skin equivalent by LC Sciences (Houston, TX). This work was supported in part by R01GM112945 and 1R01AI125366 (to IB), K01AR072773 (to BEPW), NIH K01AR072129 (to LCT), the Dermatology Foundation, the National Psoriasis Foundation, and the Arthritis National Research Foundation (to LCT).
Publisher Copyright:
© 2021 The Authors
PY - 2022/5
Y1 - 2022/5
N2 - Differences in the morphology and physiology of darkly pigmented skin compared with those of lightly pigmented skin are well-recognized. There are also disparities in the 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 as White non-Hispanic (WNH). Extensively validated RNA-sequencing analysis identified 570 differentially expressed genes in AA skin, including Igs and their receptors such as FCER1G; proinflammatory genes such as TNFα and IL32; and epidermal differentiation cluster and keratin genes. Differentially expressed genes were functionally enriched for inflammatory responses, keratinization, and cornified envelope formation. RNA-sequencing analysis of three-dimensional human skin equivalents made from AA and WNH primary keratinocytes revealed 360 differentially expressed genes (some shared with skin) that were enriched by similar functions. AA human skin equivalents appeared more responsive to TNF-α proinflammatory effects. Finally, AA-specific differentially expressed genes in the skin and human skin equivalents significantly overlapped with molecular signatures of skin in patients with atopic dermatitis and psoriasis. Overall, these findings suggest the existence of intrinsic proinflammatory 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.
AB - Differences in the morphology and physiology of darkly pigmented skin compared with those of lightly pigmented skin are well-recognized. There are also disparities in the 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 as White non-Hispanic (WNH). Extensively validated RNA-sequencing analysis identified 570 differentially expressed genes in AA skin, including Igs and their receptors such as FCER1G; proinflammatory genes such as TNFα and IL32; and epidermal differentiation cluster and keratin genes. Differentially expressed genes were functionally enriched for inflammatory responses, keratinization, and cornified envelope formation. RNA-sequencing analysis of three-dimensional human skin equivalents made from AA and WNH primary keratinocytes revealed 360 differentially expressed genes (some shared with skin) that were enriched by similar functions. AA human skin equivalents appeared more responsive to TNF-α proinflammatory effects. Finally, AA-specific differentially expressed genes in the skin and human skin equivalents significantly overlapped with molecular signatures of skin in patients with atopic dermatitis and psoriasis. Overall, these findings suggest the existence of intrinsic proinflammatory 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.
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U2 - 10.1016/j.jid.2021.09.031
DO - 10.1016/j.jid.2021.09.031
M3 - Article
C2 - 34757068
AN - SCOPUS:85121744323
SN - 0022-202X
VL - 142
SP - 1360-1371.e15
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 5
ER -