What is IL-9?

IL-9 is a multifunctional cytokine that belongs to the cytokine receptor gamma chain-dependent family of cytokines which include IL-2, IL-4, IL-7, IL-15, and IL-21. It is produced by a variety of cells, including mast cells, NKT cells, Th2, Th17, Treg, innate lymphoid cells (ILC) 2, and Th9 cells, and involved in the regulation of many kinds of cell functions. Originally, IL-9 was identified as a growth factor of T cells and mast cells. It promotes the proliferation of T lymphocytes, mast cells, erythroid precursor cells, and megakaryoblastic leukemia cell lines. Also, IL-9 has been indicated to regulate differentiation of TH17 cells and Treg function, promote class-switching to IgE in B cells, and alter haematopoietic progenitor cell activity.

As a pro-inflammatory cytokine, IL-9 is associated with the pathogenesis of multiple autoimmunity and inflammatory diseases. The increased IL-9 levels in the lung resulted in bronchial hyperresponsiveness and airway inflammation. Over-expression of IL-9 was associated with the pathogenesis of anaplastic lymphoma and Hodgkin’s disease. In addition to the pro-tumor effect, IL-9 also exerts antitumor properties in solid tumors such as melanoma.

Roles of IL-9-producing γδ T cells

IL-9 is also secreted by Vδ2 T cells, the main cell population of γδ T cell subset. Vδ2 T cells have been shown to strongly induce to express IL-9 upon in vitro activation in the presence of TGF-β/IL-15, but an absence of exogenous IL-4. Vδ2 T cells are considered as a major source of IL-9 in human peripheral blood. In the tumor, Vδ2 T cells may play an important role in antitumor immunity by producing a large amount of IL-9. Thus, IL-9-producing Vδ2 T cells may provide a promising target for tumor treatment, with enhanced therapeutic efficacy. Furthermore, IL-9-producing Vδ2 T cells may be associated with the progression of allergic diseases via promoting IgE production in B cells.

Anti-tumor effect of IL-9 and IL-9-producing cells.Fig.1 Anti-tumor effect of IL-9 and IL-9-producing cells. (Wan, 2020)

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  1. Wan, J.; et al. IL-9 and IL-9-producing cells in tumor immunity. Cell Communication and Signaling. 2020, 18: 50.
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