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- Title
Fn14 deficiency protects lupus-prone mice from histological lupus erythematosus-like skin inflammation induced by ultraviolet light.
- Authors
Doerner, Jessica; Chalmers, Samantha A.; Friedman, Adam; Putterman, Chaim
- 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 Fn14 KO mice, as compared to Fn14 WT. Furthermore, we identified several macrophage-derived proinflammatory chemokines with elevated expression in MRL/lpr mice after UV exposure. Depletion of macrophages, using a CSF-1 R inhibitor, was found to be protective against the development of skin lesions after UVB exposure. In combination with the phenotype of the MRL/lpr Fn14 KO 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.
- Subjects
FIBROBLAST growth factors; LUPUS erythematosus; SKIN inflammation; PHYSIOLOGICAL effects of ultraviolet radiation; TUMOR necrosis factors; PREVENTION
- Publication
Experimental Dermatology, 2016, Vol 25, Issue 12, p969
- ISSN
0906-6705
- Publication type
Article
- DOI
10.1111/exd.13108