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Inflammatory mediators suppress FGFR2 expression in human keratinocytes to promote skin inflammation

ABSTRACT: FGFs are key orchestrators of development, tissue homeostasis and repair. FGFR deficiency in mouse keratinocytes causes an inflammatory skin phenotype resembling atopic dermatitis (AD). To determine the human relevance of this finding, we generated human keratinocytes with a CRISPR/Cas9-induced knockout of FGFR2. Loss of this receptor promoted the expression of interferon-stimulated genes and other genes involved in inflammation under homeostatic conditions and in particular in response to inflammatory mediators without affecting cell viability. Bioinformatics analyses and functional studies showed strong down-regulation of FGFR2 expression in cultured keratinocytes exposed to various pro-inflammatory stimuli and in keratinocytes of lesional AD skin, which is likely to further aggravate the inflammatory phenotype. These results reveal a key function of FGFR2 in human keratinocytes in the suppression of skin inflammation and suggests a role of FGFR2 down-regulation in AD pathogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE267530 | GEO | 2024/08/29

REPOSITORIES: GEO

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