Titel
FAM3C/ILEI protein is elevated in psoriatic lesions and triggers psoriasiform hyperproliferation in mice
Autor*in
Iva Vokic
Center for Cancer Research, Medical University of Vienna, Comprehensive Cancer Center
... show all
Abstract
FAM3C/ILEI is an important cytokine for tumor progression and metastasis. However, its involvement in inflammation remains elusive. Here, we show that ILEI protein is highly expressed in psoriatic lesions. Inducible keratinocyte‐specific ILEI overexpression in mice (K5‐ILEIind) recapitulates many aspects of psoriasis following TPA challenge, primarily manifested by impaired epidermal differentiation and increased neutrophil recruitment. Mechanistically, ILEI triggers Erk and Akt signaling, which then activates STAT3 via Ser727 phosphorylation. Keratinocyte‐specific ILEI deletion ameliorates TPA‐induced skin inflammation. A transcriptomic ILEI signature obtained from the K5‐ILEIind model shows enrichment in several signaling pathways also found in psoriasis and identifies urokinase as a targetable enzyme to counteract ILEI activity. Pharmacological inhibition of urokinase in TPA‐induced K5‐ILEIind mice results in significant improvement of psoriasiform symptoms by reducing ILEI secretion. The ILEI signature distinguishes psoriasis from healthy skin with uPA ranking among the top “separator” genes. Our study identifies ILEI as a key driver in psoriasis, indicates the relevance of ILEI‐regulated genes for disease manifestation, and shows the clinical impact of ILEI and urokinase as novel potential therapeutic targets in psoriasis.
Stichwort
ILEI/FAM3Cinflammationkeratinocyte differentiationpsoriasisuPA/PLAU
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
phaidra.univie.ac.at/o:2064229
Erschienen in
Titel
EMBO Molecular Medicine
Band
15
Ausgabe
7
ISSN
1757-4676
Erscheinungsdatum
2023
Publication
Springer Science and Business Media LLC
Fördergeber
Europäische Union (alle Programme) — 694883
Europäische Union (alle Programme) — 766214
Erscheinungsdatum
2023
Zugänglichkeit
Rechte
Rechteangabe
© 2023 The Authors
Universität Wien | Universitätsring 1 | 1010 Wien | T
+43-1-4277-0