Uncovered role of Th9 and IL-9 in rheumatoid arthritis: Current status and future directions

Early studies on T helper (Th) 9 cells and their specific cytokine IL-9 mainly focused on the field of allergic diseases. In addition to pathological studies, IL-9 can also affect the normal development and various functions of T cells and B cells. In recent years, a series of studies have found that IL-9 may play a pathogenic role in a range of autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and multiple sclerosis (MS). Specifically, Th9 cells and IL-9 show abnormally high expression in peripheral blood, synovial fluid, and synovial tissue of patients with RA. Based on this, therapeutic strategies targeting IL-9, such as monoclonal antibodies, have become potential treatments for RA. However, research on Th9 and IL-9 in RA has only been conducted for less than two decades, and many issues are worth further exploration. This article reviews the molecular mechanisms underlying the pathogenic effects of Th9 and IL-9 in RA, summarizes the potential reasons for inducing abnormally high expression of Th9 and IL-9 in RA, and discusses future research directions. The existing evidence shows that Th9-derived IL-9 is a potential biomarker or therapeutic target in RA. We hope that this current review can play a bridging role and provide new ideas for the study of Th9 and IL-9 in RA.