Fn14 deficiency protects lupus-prone mice from histological lupus erythematosus-like skin inflammation induced by ultraviolet light

Jessica Doerner, Samantha A. Chalmers, Adam Friedman, Chaim Putterman

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

The cytokine TNF-like weak inducer of apoptosis (TWEAK) and its receptor Fn14 are involved in cell survival and cytokine production. The TWEAK/Fn14 pathway plays a role in the pathogenesis of spontaneous cutaneous lesions in the MRL/lpr lupus strain; however, the role of TWEAK/Fn14 in disease induced by ultraviolet B (UVB) irradiation has not been explored. MRL/lpr Fn14 knockout (KO) was compared to MRL/lpr Fn14 wild-type (WT) mice following exposure to UVB. We found that irradiated MRL/lpr KO mice had significantly attenuated cutaneous disease when compared to their WT counterparts. There were also fewer infiltrating immune cells (CD3+, IBA-1+ and NGAL+) in the UVB-exposed skin of MRL/lpr Fn14KO mice, as compared to Fn14WT. Furthermore, we identified several macrophage-derived proinflammatory chemokines with elevated expression in MRL/lpr mice after UV exposure. Depletion of macrophages, using a CSF-1R inhibitor, was found to be protective against the development of skin lesions after UVB exposure. In combination with the phenotype of the MRL/lpr Fn14KO mice, these findings indicate a critical role for Fn14 and recruited macrophages in UVB-triggered cutaneous lupus. Our data strongly suggest that TWEAK/Fn14 signalling is important in the pathogenesis of UVB-induced cutaneous disease manifestations in the MRL/lpr model of lupus and further support this pathway as a possible target for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)969-976
Number of pages8
JournalExperimental Dermatology
Volume25
Issue number12
DOIs
StatePublished - Dec 1 2016

Keywords

  • MRL-lpr/lpr
  • TNF-like weak inducer of apoptosis
  • cutaneous lupus
  • macrophages
  • photosensitivity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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