T helper type 9 (Th9) cells are a distinct subpopulation of CD4+ effector T cell that preferentially secretes high levels of IL-9, CCL17, CCL22, and IL-10 (in mouse). Following activation, naive CD4+ T cells differentiate into Th9 cells in the presence of TGF-beta and IL-4. These cytokines induce expression of the transcription factors PU.1/Spi-1 and Interferon Regulatory Factor 4 (IRF4), which subsequently regulate expression of the IL-9 gene. Under Th9-polarizing conditions, additional cytokines have also been shown to either enhance Th9 differentiation (IL-1 beta, IL-6, IL-21, type I interferons), or promote IL-9 secretion (IL-25, IL-2). Although the signaling molecules and transcription factors involved in Th9 differentiation are still being investigated, it is recognized that Th9 cells are closely related to Th2 cells, and there is considerable plasticity between the two cell types. Unlike Th2 cells, however, Th9 cells do not express IL-4, IL-5, or IL-13. Th9 cells are important for host defense against parasitic helminth infections, but may also have detrimental effects including contributing to the development of chronic allergic inflammation, airway remodeling, and autoimmune disease.