The immunoregulatory cytokine interleukin 10 (IL-10) is expressed mainly by T helper type 2 (TH 2) cells but also by TH 1 cells during chronic infection. Here we observed plasticity in the expression of IL-10 and IL-13 after chronic TH 1 stimulation; furthermore, the expression of Il10 and Il13 was regulated by the transcription factor E4BP4. Chronically stimulated E4BP4-deficient (Nfil3 -/-; called 'E4bp4 -/- ' here) TH 1 cells, regulatory T cells (T reg 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 TH 1 cells. E4bp4-/- TH 2 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 TH 1 cells and IL-10 in TH 1 cells, TH 2 cells, Treg cells and NKT cells.
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