IL9

Interleukin-9 (IL-9) is a cytokine in the IL-2 family that plays a role in inflammation and host defense. The IL9 gene encodes this four-helix bundle protein and, in humans, the gene is located on chromosome 5. IL-9 is produced mainly by T helper 9 (Th9) cells and by mast cells, with expression reported in other immune cells under certain conditions.

IL-9 signals through a heterodimeric receptor composed of the IL-9Rα chain and the common gamma chain (γc, CD132), which it shares with several other cytokine receptors. Upon binding, the receptor activates intracellular kinases such as JAK1 and JAK3, leading to transcriptional changes via STAT1, STAT3 and STAT5, and, in some contexts, engagement of MAPK and PI3K pathways. This signaling promotes the survival and function of the responding cells.

Th9 differentiation is driven by cytokines such as IL-4 and transforming growth factor-beta (TGF-β). In mucosal tissues, IL-9 production can be upregulated during helminth infections and allergic inflammation. Mast cells can also contribute to local IL-9 levels, amplifying immune responses in affected tissues.

Functionally, IL-9 supports growth and survival of several cell types, notably T cells and mast cells. In the airways, it promotes goblet cell hyperplasia and mucus production, contributing to airway hyperresponsiveness. It also participates in anti-helminth immunity and can modulate antibody responses in some contexts. The cytokine thus acts as a mediator of allergic inflammation and mucosal defense.

Clinically, IL-9 has been linked to asthma and other allergic conditions, with higher levels observed in some patients. Therapeutic strategies targeting IL-9 have been explored, but results have varied, and research continues to clarify its role and potential as a treatment target.