Drug Design, Development and Therapy (Apr 2022)
Therapeutic Potential of Janus Kinase Inhibitors for the Management of Interstitial Lung Disease
Abstract
Rongxiu Huo,1,* Qianyu Guo,1,* Junping Hu,2 Na Li,1 Rui Gao,1 Liangyu Mi,1 Zhaoliang Zhang,1 Hechao Liu,1 Zhiying Guo,1 Hanxi Zhao,3 Liyun Zhang,1 Ke Xu1 1Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences; Tongji Shanxi Hospital, Department of Rheumatology and Immunology, Taiyuan, 030032, People’s Republic of China; 2Department of Immunology, Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 3SILC Business School, Shanghai University, Shanghai, 200444, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ke Xu, Email [email protected]: Interstitial lung disease (ILD) refers to a heterogeneous group of diseases characterized by lung fibroblast proliferation, interstitial inflammation, and fibrosis-induced lung damage. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is known to be activated by pro-fibrotic/pro-inflammatory cytokines such as IL-6 and IL-13, whose levels are elevated in ILD. The overexpression of growth factors such as transforming growth factor β 1 in ILD activates the JAK/STAT pathway through classical or non-classical pathways, promotes macrophage activation, increases the release of pro-inflammatory and pro-fibrosis factors, and facilitates fibroblast differentiation into myofibroblasts. These findings implicate that the JAK/STAT pathway plays an important role in the course of ILD. Recent evidence also suggests that JAK inhibition alleviates excessive inflammation and pulmonary fibrosis. Accordingly, the JAK inhibitors may serve as promising drugs for the treatment of JAK/STAT-induced ILD.Keywords: interstitial lung disease, Janus kinase, signal transducers and activators of transcription, JAK inhibitor, animal model
