The World according to IL-9

Abstract

Among the cytokines regulating immune cells, IL-9 has gained considerable attention for its ability to act on multiple cell types as a regulator of beneficial and pathologic immune responses. Yet, it is still not clearly defined how IL-9 impacts immune responses. IL-9 demonstrates a remarkable degree of tissue-specific functionality and has cellular sources that vary by tissue site and the context of the inflammatory milieu. Here, we provide perspective to summarize the biological activities of IL-9 and highlight cell type–specific roles in the immune pathogenesis of diseases. This perspective will be important in defining the diseases where targeting IL-9 as a therapeutic strategy would be beneficial and where it has the potential to complicate clinical outcomes.

Vernal Keratoconjunctivitis: Immunopathological Insights and Therapeutic Applications of Immunomodulators

“…It can induce the hyperplasia of goblet cells located in the conjunctival epithelium, as well as induce the hypersecretion of mucin from these activated conjunctival goblet cells [ 4 , 74 , 90 ]. Furthermore, IL-9 also induces the hyperplasia of goblet cells [ 91 ]. Additionally, mucoid discharge has been shown to occur when histamine binds to histamine receptors expressed on goblet cells [ 74 , 92 ].…”

Cytokines in Allergic Conjunctivitis: Unraveling Their Pathophysiological Roles

“…IL-9 is a pleiotropic cytokine produced by Th9 cells [ 15 ], mast cells [ 81 ], and eosinophils [ 82 ]. Th2 cells and basophils are other cellular sources of IL-9 [ 83 ]. IL-9 is a 14 kDa glycoprotein that belongs to the four-helix bundle cytokine family [ 153 ].…”

“…IL-9 receptors (IL-9R) are expressed on epithelial cells, fibroblasts, granulocytes, lymphocytes, macrophages, and mast cells [ 84 , 85 ]. This receptor is also reported to be expressed on T cells, smooth muscle cells [ 54 ], and B cells [ 83 ]. IL-9 binds to and activates the IL-9 heterodimeric receptor complex (CD129) that consists of IL-9R alpha chain and IL-2R chain (CD132) ( Table 1 ) [ 84 ].…”

“…IL-9 is a T cell and mast cell growth factor that plays a role in the disease process of allergic inflammation [ 83 ]. It is of note that mast cells are the major targets of IL-9 produced by Th9 cells during allergic inflammation [ 83 , 154 ]. IL-9 signaling via its receptor expressed on mast cells induces the activation, proliferation, and migration of mast cells during allergen challenge [ 84 ].…”

“…Sismanopoulos et al demonstrated that IL-9 can induce mast cells to secrete vascular endothelial growth factor (VEGF) [ 132 ]. IL-9 induces the secretion of chemokine from epithelial cells and promotes the hyperplasia of goblet cells [ 83 ] located in the conjunctival layer. Interaction of IL-9 with its receptor on eosinophils induces the upregulation of IL-5R alpha chain expression on eosinophils [ 133 ].…”