Wenxia Wang, Swarna Bale, Jun Wei, Bharath Yalavarthi, Dibyendu Bhattacharyya, Jing Jing Yan, Hiam Abdala-Valencia, Dan Xu, Hanshi Sun, Roberta G Marangoni, Erica Herzog, Sergejs Berdnikovs, Stephen D Miller, Amr H Sawalha, Pei-Suen Tsou, Kentaro Awaji, Takashi Yamashita, Shinichi Sato, Yoshihide Asano, Chinnaswamy Tiruppathi, Anjana Yeldandi, Bettina C Schock, Swati Bhattacharyya, John Varga
In addition to autoimmune and inflammatory diseases, variants of the TNFAIP3 gene encoding the ubiquitin-editing enzyme A20 are also associated with fibrosis in systemic sclerosis (SSc). However, it remains unclear how genetic factors contribute to SSc pathogenesis, and which cell types drive the disease due to SSc-specific genetic alterations. We therefore characterize the expression, function, and role of A20, and its negative transcriptional regulator DREAM, in patients with SSc and disease models. Levels of A20 are significantly reduced in SSc skin and lungs, while DREAM is elevated...
October 26, 2022: Nature Communications