De novo fatty acid synthesis induced Sjögren’s syndrome by promoting Th17 differentiation

Abstract Primary Sjögren’s syndrome (pSS) is a chronic inflammatory autoimmune characterized by inflammatory infiltration of immune cells within lacrimal and salivary glands (SGs), which leads to the dysfunction of these exocrine glands. Th17 cells and their secreted cytokines play an important role in the pathogenesis of Sjogren’s syndrome, but the mechanism is still unclear. Recent clinical studies have found that metabolic disorders may be closely related to Sjogren’s syndrome. Our studies have also found that FASN, the key enzyme of lipid synthesis and metabolism in peripheral blood of Sjogren’s syndrome patients, is significantly elevated, and mainly expressed in Th17 cells. Fatty acid synthase (FASN) is downstream of ACC, and previous studies have shown that FASN activity influences both cancer and inflammation. However, it remains to be determined whether FASN is a viable target for Sjögren’s syndrome. Here, we demonstrate that FASN is a critical metabolic induced Sjögren’s syndrome by promoting the generation of inflammatory subsets of Th17 cells. In vivo, knocking out of FASN in Th17 cells, leads to reduction of Sjögren’s syndrome. These study demonstrate that FASN-mediated metabolism disorder of fatty acid synthesis may be a new mechanism to regulate Th17 cell function and lead to Sjogren’s syndrome, which can provide new directions and ideas for the treatment of Sjogren’s syndrome.