The present disclosure relates to methods and compositions for treating and/or preventing autoimmune fibrosis, such as systemic sclerosis (SSc scleroderma). The method includes administering to a subject in need thereof an effective amount of a death receptor agonist. Suitable death receptor agonists include tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL), agonistic death receptor antibodies, and variants, analogues, or derivatives thereof. The administration of the death receptor agonist blocks fibroblast or profibrogenic cell activation, and/or reduces or depletes myofibroblasts, thereby reducing or preventing systemic sclerosis.
