Department of Clinical & Experimental Medicine, Rheumatology Unit, University of Messina, University Hospital 'Gaetano Martino', via Consolare Valeria 1, 98100, Messina, Italy.
Immunotherapy. 2021 Feb;13(3):241-256. doi: 10.2217/imt-2020-0270. Epub 2020 Dec 2.
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.
系统性硬化症（SSc）相关间质性肺病（ILD）的发病机制仍存在争议，迄今为止尚无治疗方法被证明完全有效。细胞内 Janus 激酶（JAK）/信号转导和转录激活因子（STAT）通路在免疫或非免疫细胞中高度保守，参与炎症和纤维化。临床前研究证据表明，JAK/STAT 信号级联在自身反应性细胞的分化以及 SSc 中发生的细胞外基质重塑中起着关键作用。因此，使用口服小分子 JAK 抑制剂，特别是如果早期使用，可能会预防或减缓 SSc 相关 ILD 的进展，但目前很少有临床研究支持这一假说。
