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bioRxiv · 10.64898/2026.03.20.711763

An FGF7-FGFR2-KLF4 feedback loop sustains anti-inflammatory signaling in epithelial cells

Werner, S.·Ferrarese, L.·Wuest, D.·Bento Lopes, L.·Kucukaylak, I.·Sander, S.·Gerber, J.·Dengjel, J.
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Abstract

Chronic or excessive inflammation are hallmarks of many human diseases, but the endogenous factors that limit inflammatory responses are insufficiently characterized. We discovered a broad anti-inflammatory function of fibroblast growth factor 7 (FGF7), which is mediated via epithelial cels. FGF7 suppressed the expression of pro-inflammatory and immunomodulatory genes in cultured human keratinocytes in the absence or presence of pro-inflammatory stimuli and in a psoriasiform inflammation model in mice. Mechanistically, this involves an FGF7-FGF receptor 2 (FGFR2)-MAPK-Kruppel-like factor 4 (KLF4) signaling axis. FGF7 induced significant alterations in the KLF4 interactome in human keratinocytes and suppressed the transcriptional activity of KLF4 at its pro-inflammatory target genes. Concomitantly, expression of FGFR2 and downstream signaling components was promoted by KLF4, identifying a KLF4-dependent regulatory feedback loop that sustains anti-inflammatory FGF signaling. These results suggest activation of FGF7-FGFR2-KLF4 signaling as a strategy for the treatment of inflammatory diseases involving the skin or other epithelial tissues and highlight the role of epithelial cells in the control of inflammation.

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Werner, S., Ferrarese, L., Wuest, D., Bento Lopes, L., Kucukaylak, I., Sander, S., Gerber, J., Dengjel, J.. 2026-03-23. An FGF7-FGFR2-KLF4 feedback loop sustains anti-inflammatory signaling in epithelial cells. https://doi.org/10.64898/2026.03.20.711763

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