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Transforming growth factor-β 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9–producing subset

Abstract

Since the discovery of T helper type 1 and type 2 effector T cell subsets 20 years ago, inducible regulatory T cells and interleukin 17 (IL-17)-producing T helper cells have been added to the 'portfolio' of helper T cells. It is unclear how many more effector T cell subsets there may be and to what degree their characteristics are fixed or flexible. Here we show that transforming growth factor-β, a cytokine at the center of the differentiation of IL-17-producing T helper cells and inducible regulatory T cells, 'reprograms' T helper type 2 cells to lose their characteristic profile and switch to IL-9 secretion or, in combination with IL-4, drives the differentiation of 'TH-9' cells directly. Thus, transforming growth factor-β constitutes a regulatory 'switch' that in combination with other cytokines can 'reprogram' effector T cell differentiation along different pathways.

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Figure 1: TGF-β and IL-4 drive 'TH-9' differentiation.
Figure 2: IL-9 expression distinct from that of the profiles of TH1, TH2, iTreg and TH-17 effector cells.
Figure 3: TGF-β 'reprograms' committed TH2 cells to a 'TH-9' profile.
Figure 4: TGF-β responsiveness is essential for IL-9 production in vivo.

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Acknowledgements

We thank A. Rae and G. Preece for cell sorting; I. Baar for testing the specificity of goat anti-IL-9 by ELISA; and C. Watson (University of Cambridge) for spleens from Stat6−/− mice on a BALB/c background. Supported by the Fonds National de la Recherche Scientifique, Belgium (C.U. and J.v.S.).

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Authors and Affiliations

Authors

Contributions

M.V. did and designed the experiments; C.U. and J.v.S. generated and labeled IL-9-specific monoclonal and polyclonal antibodies and did ELISA; H.H. did the trichuris experiments; B.M. contributed to experiments on deviation; A.W. and J.B. did the microarray analyses that were the starting basis of these studies; and B.S. designed experiments and wrote the manuscript.

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Correspondence to Brigitta Stockinger.

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Veldhoen, M., Uyttenhove, C., van Snick, J. et al. Transforming growth factor-β 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9–producing subset. Nat Immunol 9, 1341–1346 (2008). https://doi.org/10.1038/ni.1659

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