Fn14 deficiency protects lupus‐prone mice from histological lupus erythematosus‐like skin inflammation induced by ultraviolet light. Issue 12 (29th November 2016)

• Record Type: Journal Article
• Authors: Doerner, Jessica; Chalmers, Samantha A.; Friedman, Adam; Putterman, Chaim
• Other Names: Wolf Peter guestEditor.; de Gruijl Frank guestEditor.
• Is Part Of: Experimental dermatology. Volume 25:Issue 12(2016)
• Page Start: 969
• Page End: 976
• Publication Date: 2016-11-29
• Subjects: cutaneous lupus -- macrophages -- MRL‐lpr/lpr -- photosensitivity -- TNF‐like weak inducer of apoptosis; Dermatology -- Periodicals; 616.5
• DOI: 10.1111/exd.13108
• Languages: English
• ISSNs: 0906-6705

Abstract

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.