Some cytokines refuse to be pigeonholed. On page 1653, Nowak et al. show that interleukin (IL) 9 can derive from a number of CD4+ T cell types. And when produced in an autoimmune setting, IL-9 contributed to disease.
Many types of CD4+ T cells, including Th2 and regulatory T cells, produce IL-9 in response to TGF-β. And despite earlier reports to the contrary, Nowak and colleagues now find that this also holds true for Th17 cells. In fact, Th17 cells produced more IL-9 in culture in response to TGF-β than did other types of CD4+ T cells.
In the absence of IL-9 signals, mice were partially protected against EAE, a Th17-driven autoimmune disease that models multiple sclerosis. These mice had fewer IL-17– and IL-6–producing cells in the CNS and fewer mast cells in draining lymph nodes. IL-9 is known to enhance mast cell recruitment, and mast cells have been shown to contribute to EAE. However, in other contexts, the cytokine appears to suppress, rather than exacerbate, inflammation.
As for recent claims regarding which lineages can or cannot secrete IL-9, the authors suggest that diet may influence cytokine secretion, perhaps accounting for conflicting results. Diets high in vitamin A raise retinoic acid levels, and the authors have initial evidence that retinoic acid inhibits IL-9 secretion. AM
