New Posttranslational Modification Lactylation Brings New Inspiration for the Treatment of Rheumatoid Arthritis

Yue Yang,1,* Jinjie Shi,2,* Jiming Yu,3,* Xin Zhao,1 Ke Zhu,1 Shen Wang,4 Xinwen Zhang,1 Xieyu Zhang,1 Guangcheng Wei,1 Wei Cao1 1Rheumatology Department, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Graduate School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3The Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 4Orthopedics Department, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Cao, Wangjing Hospital of China Academy of Chinese Medical Sciences, 6 South Central Road, Chaoyang District, Beijing, 100102, People’s Republic of China, Email [email protected]: Lactic acid (LA) is an essential glycolytic metabolite and energy source in the body, which is present in high levels in the synovial fluid of patients with rheumatoid arthritis (RA) and is a reliable indicator for identifying inflammatory arthritis. LA not only acts as an inflammatory amplifier in RA, recent studies have found that novel posttranslational modification (PTM) lactylation mediated by LA may also play a key role in RA. Single-cell sequencing showed that the RA lactylation score of patients with RA was significantly increased, and core lactylation-promoting genes, including NDUFB3, NGLY1, and other genes, were found to be potential biomarkers of RA. More studies have shown that lactylation can regulate genes in various cells, such as fibroblast-like synoviocytes (FLSs) and macrophages, thus playing a special role in the development and occurrence of autoimmune diseases, neurological diseases, and cancer diseases. In this paper, we review the research on lactylation in RA-related cells and mechanisms and bring new insights into the pathogenesis, diagnosis, and treatment of RA.Keywords: lactic acid, lactylation, posttranslational modification, rheumatoid arthritis