Yoking OX40 to regulation of IL-9

Abstract

The secretion of cytokines by helper T cells is affected by the cytokine environment and by costimulatory signals. Engagement of the receptor OX40 on T cells increases expression of the transcription factor TRAF6, activates the alternative transcription factor NF-κB pathway and induces the production of interleukin 9.

Figure 1

OX40 induces IL-9 in differentiating T_H9 cells. (a) OX40L expressed on an antigen-presenting cell (APC) engages OX40 on the surface of a T cell. In the context of activation of the antigen receptor and T_H9-polarizing cytokines, engagement of OX40 results in the induction of Il9. (b) Despite the engagement of OX40 in T_H9 cultures that results in activation of the canonical and noncanonical NF-κB pathways, only the noncanonical pathway induces Il9. TRAF6 has an obligatory role in activation of the noncanonical pathway. RelB-p52 heterodimers are bound to NF-κB consensus sequences in the Il9 promoter, indicated by numbers that are relative to the transcriptional start site. NIK and IKK are kinases; IκB is an inhibitor of NF-κB; p100 is the precursor of p52.