The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4+ T cells

Abstract

Chronic stimulation of lymphocytes results in upregulation of immunomodulatory IL-10, but the molecular mechanisms of this process have remained unknown. Kubo and colleagues demonstrate that the transcription factor E4BP4 is responsible for this plasticity. The immunoregulatory cytokine interleukin 10 (IL-10) is expressed mainly by T helper type 2 (TH2) cells but also by TH1 cells during chronic infection. Here we observed plasticity in the expression of IL-10 and IL-13 after chronic TH1 stimulation; furthermore, the expression of Il10 and Il13 was regulated by the transcription factor E4BP4. Chronically stimulated E4BP4-deficient (Nfil3−/−; called 'E4bp4−/−' here) TH1 cells, regulatory T cells (Treg cells) and natural killer T cells (NKT cells) had attenuated expression of IL-10 and IL-13. Enforced expression of E4bp4 initiated the production of IL-10 and IL-13 by conventional TH1 cells. E4bp4−/− TH2 cells showed impairment of IL-10 production with no effect on IL-13. Our results indicate that E4BP4 has multiple functions in controlling the plasticity of IL-13 in TH1 cells and IL-10 in TH1 cells, TH2 cells, Treg cells and NKT cells.