The rationale for targeting the JAK/STAT pathway in scleroderma-associated interstitial lung disease

The etiopathogenesis of systemic sclerosis (SSc)-associated interstitial lung disease (ILD) is still debated and no therapeutic options have proved 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/STAT signaling cascade has a crucial role in the differentiation of autoreactive cells as well as in the extracellular matrix remodeling that occurs in SSc. Therefore, it is likely that the use of oral small molecule JAK-inhibitors, especially if prescribed early, may prevent or slow the progression of SSc-associated ILD, but few clinical studies currently support this hypothesis.