Modulation of cytokine receptors by IL-2 broadly regulates differentiation into helper T cell lineages

W Liao, JX Lin, L Wang, P Li, WJ Leonard - Nature immunology, 2011 - nature.com
W Liao, JX Lin, L Wang, P Li, WJ Leonard
Nature immunology, 2011nature.com
Helper T cells control host defense against pathogens. The receptors for interleukin 12 (IL-
12), IL-4 and IL-6 are required for differentiation into the TH1, TH2 and TH17 subsets of
helper T cells, respectively. IL-2 signaling via the transcription factor STAT5 controls TH2
differentiation by regulating both the TH2 cytokine gene cluster and expression of Il4ra, the
gene encoding the IL-4 receptor α-chain. Here we show that IL-2 regulated TH1
differentiation, inducing STAT5-dependent expression of the IL-12 receptor β2-chain (IL …
Abstract
Helper T cells control host defense against pathogens. The receptors for interleukin 12 (IL-12), IL-4 and IL-6 are required for differentiation into the TH1, TH2 and TH17 subsets of helper T cells, respectively. IL-2 signaling via the transcription factor STAT5 controls TH2 differentiation by regulating both the TH2 cytokine gene cluster and expression of Il4ra, the gene encoding the IL-4 receptor α-chain. Here we show that IL-2 regulated TH1 differentiation, inducing STAT5-dependent expression of the IL-12 receptor β2-chain (IL-12Rβ2) and the transcription factor T-bet, with impaired human TH1 differentiation when IL-2 was blocked. TH1 differentiation was also impaired in mouse Il2−/− T cells but was restored by IL-12Rβ2 expression. Consistent with the inhibition of TH17 differentiation by IL-2, treatment with IL-2 resulted in lower expression of the genes encoding the IL-6 receptor α-chain (Il6ra) and the IL-6 signal transducer gp130 (encoded by Il6st), and retroviral transduction of Il6st augmented TH17 differentiation even when IL-2 was present. Thus, IL-2 influences helper T cell differentiation by modulating the expression of cytokine receptors to help specify and maintain differentiated states.
nature.com