Il9, or Interleukin-9, is a multifunctional cytokine. It is involved in a variety of biological processes and plays significant roles in many diseases. IL-9 is transcriptionally regulated by non-coding regulatory elements around the Il9 gene, and its-promoting transcription factors can bind these elements to modulate gene expression [3]. IL-9 is produced by multiple cell types such as T cells, basophils, and mast cells, and is an important mediator in allergic diseases, being critical for mast-cell-driven diseases [2].

In a collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis (CIA) model, interventions targeting Il9 substantially mitigated the inflammatory phenotype in rheumatoid arthritis, indicating its pro-inflammatory role, especially in macrophage and fibroblast-like synoviocyte hyperactivation [1]. In a food allergy model, Il9 CNS-25, a regulatory element of the Il9 gene, is required for IL-9 production from T cells, basophils, and mast cells, and deficiency in IL-9 expression leads to decreased mast cell expansion [2]. Neutralization of IL-9 along with IL-6 enhanced host survivability and reduced the mean neurological score in experimental cerebral malaria, and also down-regulated the frequency of Th17 cells and related transcription factors [4]. Anti-IL9 treatment alleviated trinitrobenzene sulfonic acid (TNBS)-induced colitis by restoring Claudin 8 (CLDN8) levels in the colonic mucosa in the context of inflammatory bowel disease [5].

In conclusion, Il9 is a key cytokine involved in multiple biological processes and diseases. Studies using gene-knockout mouse models have revealed its roles in diseases such as rheumatoid arthritis, allergic diseases, experimental cerebral malaria, and inflammatory bowel disease. These findings highlight the importance of Il9 as a potential therapeutic target in these disease areas.