Th9 cells and IL-9 in autoimmune disorders: Pathogenesis and therapeutic potentials

Naïve CD4⁺ T cells are pleiotropically divided into various T helper (Th) cell subsets, according to their pivotal roles in the regulation of immune responses. The differentiation of Th9 cells, an interleukin (IL)-9 producing subset, can be impacted by specific environmental cues, co-stimulation with transforming growth factor β (TGF-β) and IL-4, and other regulatory factors. Although IL-9 has been recognized as a classical Th2-related cytokine, recent studies have indicated that IL-9-producing cells contribute to a group of autoimmune disorders including systemic lupus erythematosus (SLE), multiple sclerosis (MS), inflammatory bowel diseases (IBD), rheumatoid arthritis (RA) and psoriasis. Studies of Th9 cells in autoimmune diseases, although in their infancy, are expected to be of growing interest in the study of potential mechanisms of cytokine regulatory pathways and autoimmune pathogenesis. Several in vitro and in vivo pre-clinical trials have been conducted to explore potential therapeutic strategies by targeting the IL-9 pathway. Specifically, anti-IL-9 monoclonal antibodies (mAbs) and IL-9 inhibitors may potentially be used for the clinical treatment of allergic diseases, autoimmune diseases or cancers. Here, we review recent research on Th9 cells and IL-9 pertaining to cell differentiation, biological characteristics and pivotal cellular inter-relationships implicated in the development of various diseases.