IL-9 binds to the IL-9 receptor (IL-9R), which dimerizes with the common gamma chain (γc) to activate JAK/STAT, MAPK, and PI3K pathways . Key roles include:
Immune Cell Regulation: Enhances mast cell survival, Th9/Th17 differentiation, and Treg suppressive activity .
Inflammatory Modulation: Drives IgE production, eosinophil recruitment, and mucus metaplasia in asthma models .
Dual Roles in Cancer: Promotes antitumor immunity via mast cell activation but may suppress immune responses via Treg recruitment .
Asthma: IL-9 induces bronchial hyperresponsiveness and mucus overproduction in murine asthma models .
Cancer: In B16F10 melanoma and Lewis Lung carcinoma models, IL-9 reduces tumor growth via mast cell-dependent mechanisms .
Autoimmunity: IL-9 fusion proteins targeting fibronectin EDA delay arthritis progression in collagen-induced models .
Proliferation Assays: ED₅₀ values of 0.382–5.0 ng/mL in MO7e and Th9 cell lines .
Targeted Delivery: Antibody-IL9 fusions (e.g., F8-IL9) achieve tumor:blood ratios >10:1 in biodistribution studies .
Therapeutic Efficacy: While IL-9 enhances antitumor immunity in melanoma , recent studies show minimal therapeutic impact in CT26 and F9 teratocarcinoma models at tolerated doses .
Innate vs. Adaptive Sources: IL-9 production in papain-induced lung inflammation is innate lymphoid cell (ILC)-dependent but requires adaptive immune-derived IL-2 for sustained expression .
Th9 Differentiation: TGF-β reprograms Th2 cells to IL-9-secreting Th9 cells, linking IL-9 to chronic inflammation .
Mast Cell Dependency: IL-9’s antitumor effects in melanoma require mast cells but not T/B cells .
Arthritis Resolution: Hydrodynamic IL-9 gene delivery reduces bone loss in murine arthritis via ILC2-Treg crosstalk .