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TWEAK participates in various cellular effects by engaging its receptor of Fn14. Increased levels of soluble TWEAK are associated with systemic autoimmunity in patients with lupus erythematosus, rheumatoid arthritis, or dermatomyositis. However, the role of TWEAK in bullous pemphigoid (BP) remains unknown. In this study, we found an elevated serum level of TWEAK and a positive correlation between serum TWEAK and anti-BP180 antibodies. Immunohistochemistry showed strong TWEAK and Fn14 expression and implied an opposite relationship between the TWEAK and BP180 expression in skin samples from BP patients. In vitro TWEAK stimuli reduced BP180 expression in HaCaT cells and inhibited the adhesion of cells to the culture dish. Consistently, the transfection of Fn14 small interfering RNA preserved BP180 and protected cells from losing adherence. Moreover, such effect of TWEAK correlated with …