A brief history of IL-9

Abstract

IL-9 was first described in the late 1980s as a member of a growing number of cytokines that had pleiotropic functions in the immune system. Although many biological functions have been attributed to IL-9, it remains an understudied cytokine. A resurgence of interest in IL-9 has been spurred by recent work demonstrating a role for IL-9 in regulating inflammatory immunity and defining the transcription factors that activate the Il9 gene in cells that most efficiently produce IL-9. In this review, we summarize the characterization of IL-9 biological activities, highlight roles for the cytokine that are clearly defined, and outline questions regarding IL-9 functions that still require further exploration.

Figure 1

Transcription factor activation of the gene encoding IL-9. In T cells, the most efficient priming of IL-9 production occurs in response to a combination of TGF-β and IL-4. PU.1 may be downstream of the TGF-β signal, and STAT6 and GATA3, both required for the development of IL-9-secreting T cells, are downstream of IL-4. IRF4 expression may be regulated by both signals. It is not known if STAT6 or GATA3 binds the Il9 gene directly. PU.1 and IRF4 bind the Il9 promoter directly in Th9 cells. AP1, and NF-κB bind the promoter in response to TLR stimulation in mast cells, and are likely downstream of IL-1 and IL-25 signaling in T cells.

Figure 2

IL-9 is a pleiotropic cytokine. IL-9 has direct and indirect effects on multiple cell types that affect the development of immunity and inflammation.