From interleukin-9 to T helper 9 cells

Interleukin-9 (IL-9), cloned more than 20 years ago, was initially thought to be a Th2-specific cytokine. This assumption was initially confirmed by functional analyses showing that both IL-9 and Th2 cells play an important role in the pathogenesis of asthma, IgE class switch recombination, and resolution of parasitic infections. However, recently it was shown that IL-9-producing CD4(+) T cells represent the discrete T helper subset Th9 cells. Herein, we will review the cytokines and transcription factors known to promote the development of Th9 cells and their potential functional properties in relation to the biological activities of IL-9. In addition, we will discuss how Th9 cells are related to Th2, Th17, and T-reg cells, as both an alternative source of IL-9 and in view of the fact that plasticity of CD4(+) T cell differentiation is currently a strong matter of debate in immunologic research.