Fibroblast growth factor receptors 1 and 2 in keratinocytes control the epidermal barrier and cutaneous homeostasis

Jingxuan Yang, Michael Meyer, Anna Katharina Müller, Friederike Böhm, Richard Grose, Tina Dauwalder, Francois Verrey, Manfred Kopf, Juha Partanen, Wilhelm Bloch, David M. Ornitz, Sabine Werner

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

Fibroblast growth factors (FGFs) are master regulators of organogenesis and tissue homeostasis. In this study, we used different combinations of FGF receptor (FGFR)-deficient mice to unravel their functions in the skin. Loss of the IIIb splice variants of FGFR1 and FGFR2 in keratinocytes caused progressive loss of skin appendages, cutaneous inflammation, keratinocyte hyperproliferation, and acanthosis. We identified loss of FGF-induced expression of tight junction components with subsequent deficits in epidermal barrier function as the mechanism underlying the progressive inflammatory skin disease. The defective barrier causes activation of keratinocytes and epidermal γδ T cells, which produce interleukin-1 family member 8 and S100A8/A9 proteins. These cytokines initiate an inflammatory response and induce a double paracrine loop through production of keratinocyte mitogens by dermal cells. Our results identify essential roles for FGFs in the regulation of the epidermal barrier and in the prevention of cutaneous inflammation, and highlight the importance of stromal-epithelial interactions in skin homeostasis and disease.

Original languageEnglish
Pages (from-to)935-952
Number of pages18
JournalJournal of Cell Biology
Volume188
Issue number6
DOIs
StatePublished - Mar 22 2010

Fingerprint

Dive into the research topics of 'Fibroblast growth factor receptors 1 and 2 in keratinocytes control the epidermal barrier and cutaneous homeostasis'. Together they form a unique fingerprint.

Cite this