Targeting cytokines and potentiality of JAK–STAT inhibition in systemic sclerosis

Abstract

Systemic sclerosis (SSc) or scleroderma is an autoimmune disease of unknown etiology, the treatment of which has garnered increased research interest. Associated symptoms range from localized or diffused skin tightening to multiple organ failure, including the lungs, kidneys, heart, and gastrointestinal tract, with considerable morbidity and mortality. Given that several cytokines contribute to the immune pathogenesis of SSc, efforts have been made toward the development of treatments targeting these cytokines to control disease progression. Indeed, anti-cytokine therapy has emerged as a new therapeutic intervention. Recently, the Janus kinase signal transducer and activator of transcription (JAK–STAT) pathway has been investigated as a novel candidate for the fibrogenic pathology of SSc. However, a comprehensive scientific review of the targeted therapy for SSc has been hampered by the rarity and heterogeneous nature of the disease. In this review, we provide an overview of cytokines involved in the innate and adaptive immune pathogenesis of SSc based on recent scientific data. In particular, we focus on targeted anti-cytokine therapy and the emerging role of the JAK–STAT inhibitor, a prospective therapeutic agent for the reversal of disease pathogenesis.