Il9, also known as interleukin-9, is a multifunctional cytokine. It is involved in various biological processes and is associated with multiple 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 its production [3]. IL-9 plays a role in allergic diseases as it is crucial for mast-cell-driven diseases [2].

In the context of rheumatoid arthritis (RA), interventions targeting PU.1 and IL-9 in collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis (CIA) models, using PU.1-T cell-conditional knockout (KO), IL-9 KO, and IL-9R KO mice, substantially mitigated the inflammatory phenotype. IL-9 was found to have a pro-inflammatory role, especially in the hyper-activation of macrophages and fibroblast-like synoviocytes. Mechanistically, PU.1 and IL-9 form a positive feedback loop in RA [1]. In preeclampsia, decreased placental IL9 and IL9R levels impair trophoblast cell proliferation, invasion, and angiogenesis, suggesting that IL9/IL9R signaling could be a new potential therapeutic target [4].

In conclusion, Il9 is a key cytokine involved in multiple biological functions. Gene-knockout mouse models, such as IL-9 KO and IL-9R KO mice, have been instrumental in revealing its role in diseases like rheumatoid arthritis and preeclampsia. These studies provide potential therapeutic targets for treating these diseases by targeting the Il9-related pathways.