Regulation of IL-9 expression by IL-25 signaling

The physiological regulation of the expression of interleukin (IL)-9, a cytokine traditionally regarded as being T(H)2 associated, remains unclear. Here, we show that IL-9-expressing T cells generated in vitro in the presence of transforming growth factor-beta and IL-4 express high levels of mRNA for IL-17 receptor B (IL-17RB), the receptor for IL-25. Treatment of these cells with IL-25 enhances IL-9 expression in vitro. Moreover, transgenic and retroviral overexpression of IL-17RB in T cells results in IL-25-induced IL-9 production that is IL-4 independent. In vivo, the IL-25-IL-17RB pathway regulates IL-9 expression in allergic airway inflammation. Thus, IL-25 is a newly identified regulator of IL-9 expression.