Abstract
We cultured human hair follicle-derived keratinocytes (FDKs) from plucked hairs. To gain insight into gene expression signatures that can distinguish atopic dermatitis from non-atopic controls without skin biopsies, we undertook a comparative study of gene expression in FDKs from adult donors with atopic dermatitis and non-atopic donors. FDK primary cultures (atopic dermatitis, n = 11; non-atopic controls, n = 7) before and after interferon gamma (IFN-γ) treatment were used for microarray analysis and quantitative RT-PCR. Comparison of FDKs from atopic and non-atopic donors indicated that the former showed activated pathways with innate immunity and decreased pathways of cell growth, as indicated by increased NLRP2 expression and decreased DKK1 expression, respectively. Treatment with IFN-γ induced the enhanced expression of IL32, IL1B, IL8, and CXCL1 in the cells from atopic donors compared to that in cells from non-atopic donors at 24 h after treatment. IL1B expression in FDKs after IFN-γ treatment correlated with IL32 expression. We hypothesized that overexpression of IL32 in hair follicle keratinocytes of patients with atopic dermatitis would lead to the excessive production of pro-IL1β and that the activation of IL1β from pro-IL1β by inflammasome complex, in which NLRP2 protein might be involved, would be augmented. This is the first report to show enhanced induction of cytokine/chemokine genes by IFN-γ in atopic dermatitis using cultured FDKs.
Highlights
IntroductionThere are two stem cell repositories within the epidermis: the interfollicular epidermis and the hair follicle
The epidermis renews constantly throughout an individual’s lifetime
The gene expression profile of follicle-derived keratinocytes (FDKs) was similar to that of NHEKs. Both FDKs and NHEKs showed abundant expression of genes encoding structural components, molecules associated with cell-cell and cell-extracellular matrix adhesion, and proteins involved in cornification of the skin (S100 calcium-binding proteins, annexins, and cystatins) (Table S1)
Summary
There are two stem cell repositories within the epidermis: the interfollicular epidermis and the hair follicle. Hair follicle stem cells do not normally contribute to the homeostasis of the epidermis but do contribute to wound-healing following full-thickness wounds [5,6]. Cells from hair follicles are recruited into the epidermis and migrate to the wound region, but over several weeks, most of the cells from the hair follicles are eliminated from the epidermis. In this respect, hair follicle stem cells differ from interfollicular stem cells
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