The dual role of IL-27 in CD4+T cells

•IL-27’s dual role on CD4+ T cells, including on its survival, proliferation, differentiation, and function are fully summarized and analyzed.•The underlying mechanism of its dual role is associated with the following items:the time course of the immune response and disease phase, interaction between molecules and IL-27, differential activation of the downstream signal, and different experimental models.•Some suggestions for future work about IL-27’s dual role are put forward, such as chromatin remodelling, cellular localization, and post-translational modifications may also explain the dual role of IL-27. Interleukin-27 (IL-27), a member of the IL-6/IL-12 family, has diverse regulatory functions in various immune responses, and is recognised as a potent agonist and antagonist of CD4+T cells in different contexts. However, this dual role and underlying mechanisms have not been completely defined. In the present review, we summarise the dual role of IL-27 in CD4+T cells. In particular, we aimed to decipher its mechanism to better understand the context-dependent function of IL-27 in CD4+T cells. Furthermore, we propose a possible mechanism for the dual role of IL-27. This may be helpful for the development of appropriate IL-27 treatments in various clinical settings.