Fn14 deficiency protects lupus-prone mice from cutaneous lesions induced by UVB irradiation (BA6P.135)

Abstract

Abstract Cutaneous lupus erythematosus (CLE) in one of its various forms is seen in the majority of patients with systemic lupus. Photosensitivity is common in lupus, and sunlight (via UVB irradiation) is a well-recognized trigger of CLE. A TNF superfamily member, TNF-like weak inducer of apoptosis (TWEAK), is a soluble cytokine that binds to its sole known signaling receptor, Fn14. TWEAK and Fn14 are upregulated with inflammation and/or injury, and this pathway is important in critical biologic processes including angiogenesis, cell survival, and local inflammation. Previously, we found that lupus-prone MRL/lpr mice deficient for Fn14 (Fn14 KO) had markedly attenuated skin disease (which develops spontaneously in this strain) as compared to Fn14 wild-type (WT) mice. Here, we demonstrate that absence of the Fn14 receptor is protective against the expected UVB-induced eruption. MRL/lpr Fn14 WT mice developed significantly more severe skin involvement following exposure to UVB when compared to strain, age, and gender matched Fn14 KO mice. Histologically, MRL/lpr Fn14 WT mice had significantly more apoptotic keratinocytes, basement membrane degeneration, and dermal inflammation comprised of macrophages following UVB. RT-PCR revealed higher levels of CXCL9, CXCL10, CXCL11 and RANTES in MRL/lpr Fn14 WT mice. Our data suggests a novel role for the TWEAK/Fn14 signaling pathway in the induction of cutaneous lupus lesions following UVB.