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Aiolos promotes TH17 differentiation by directly silencing Il2 expression

A Corrigendum to this article was published on 18 December 2013

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Abstract

CD4+ interleukin 17 (IL-17)-producing helper T cells (TH17 cells) are instrumental in the immune response to pathogens. However, an overactive TH17 response results in tissue inflammation and autoimmunity, and therefore it is important to identify the molecular mechanisms that control the development of TH17 cells. IL-2 suppresses such development, but how IL-2 production is actively suppressed during TH7 differentiation is not understood. Here we report that under TH17-polarizing conditions, the transcription factors STAT3 and AhR upregulated the expression of Aiolos, a member of the Ikaros family of transcription factors. Using Aiolos-deficient mice, we demonstrated that Aiolos silenced the Il2 locus, promoting TH17 differentiation in vitro and in vivo. Thus, we have identified a module in the transcriptional program of TH17 cells that actively limits IL-2 production and promotes their differentiation.

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Figure 1: Expression of Aiolos by TH17 cells.
Figure 2: Aiolos controls the development of TH17 cells.
Figure 3: Aiolos limits IL-2 production in TH17 cells.
Figure 4: Aiolos silences the Il2 promoter in TH17 cells.
Figure 5: AhR and STAT3 control Aiolos expression in TH17 cells.
Figure 6: Aiolos controls the generation of IL-17-producing CD4+ memory T cells.
Figure 7: Aiolos-deficient CD4+CD25CD45RBhi T cells induce an aggressive wasting disease in Rag2−/− recipient mice.

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Change history

  • 21 September 2012

    In the version of this article initially published, some data in the bottom right plot in Figure 3d were partially obscured. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank D. Kozoriz for cell sorting, and B. Waksman and I.R. Cohen for discussions. Supported by the US National Institutes of Health (P01AI073748, P01NS038037, P01AI056299 and R01NS030843 to V.K.K.; and AI075285 and AI093903 to F.J.Q.), the National Multiple Sclerosis Society (RG4111A1 to F.J.Q.), the Harvard Medical School Office for Diversity and Community Partnership (F.J.Q.) and the National Multiple Sclerosis Society (FG1850-A-1 to H.J.).

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H.J., F.J.Q., M.N. and M.R. did in vitro and in vivo experiments; M.N., A.Y., E.J.B., D.K., C.Z. and S.X. did in vitro experiments; K.G. and J.S. provided reagents; F.J.Q. wrote the manuscript; and V.K.K. and F.J.Q. supervised the study and edited the manuscript.

Corresponding authors

Correspondence to Francisco J Quintana or Vijay K Kuchroo.

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The authors declare no competing financial interests.

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Quintana, F., Jin, H., Burns, E. et al. Aiolos promotes TH17 differentiation by directly silencing Il2 expression. Nat Immunol 13, 770–777 (2012). https://doi.org/10.1038/ni.2363

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