IL-9 and its Receptor: From Signal Transduction to Tumorigenesis

IL-9 is a multifunctional cytokine secreted by TH2 lymphocytes. Besides its role during immune responses, its growth factor and antiapoptotic activities on multiple transformed cells suggest a potential role in tumorigenesis. Indeed, IL-9 overexpression induces thymic lymphomas in mice, and IL-9 production is associated with Hodgkin disease and HTLV-I transformed T cells in humans. IL-9 activities are mediated by a specific receptor chain that forms a heterodimeric receptor with the common gamma chain also involved in IL-2,4,7,15 and 21 signaling. The IL-9 receptor and common gamma chains associate with JAK1 and JAK3, respectively and trigger the STAT-1, -3 and -5, IRS and RAS-MAPK pathways. Moreover, in vitro, dysregulated IL-9 response can lead to autonomous cell growth and malignant transformation of lymphoid cells associated with constitutive activation of the Jak/STAT pathway.