The transcription factor IRF1 dictates the IL-21-dependent anticancer functions of T(H)9 cells

The T(H)9 subset of helper T cells was initially shown to contribute to the induction of autoimmune and allergic diseases, but subsequent evidence has suggested that these cells also exert antitumor activities. However, the molecular events that account for their effector properties are elusive. Here we found that the transcription factor IRF1 enhanced the effector function of T(H)9 cells and dictated their anticancer properties. Under T(H)9-skewing conditions, interleukin 1 beta (IL-1 beta) induced phosphorylation of the transcription factor STAT1 and subsequent expression of IRF1, which bound to the promoters of II9 and II21 and enhanced secretion of the cytokines IL-9 and IL-21 from T(H)9 cells. Furthermore, IL-1 beta-induced T(H)9 cells exerted potent anticancer functions in an IRF1- and IL-21-dependent manner. Our findings thus identify IRF1 as a target for controlling the function of T(H)9 cells.