The rationale for targeting the JAK/STATpathway in scleroderma-associated interstitial lung disease.

Abstract

The etiopathogenesis of systemic sclerosis (SSc)-associated interstitial lung disease (ILD) is still debated and no therapeutic options haveproved fully effective to date. The intracellular Janus kinase (JAK)/signal transducer and activator of transcription(STAT)pathway is highly conserved among either immune or nonimmune cells and involved in inflammation and fibrosis. Evidence from preclinical studies shows that the JAK/STATsignaling cascade has a crucial role in the differentiation of autoreactive cells as well as in theextracellular matrix remodeling that occurs in SSc. Therefore, it is likely that the use oforal small moleculeJAK-inhibitors, especially if prescribed early, may prevent or slow the progression of SSc-associated ILD, but few clinical studies currently support this hypothesis.