Abstract
CD4+ helper T cells acquire effector phenotypes that promote specialized inflammatory responses. We show that the ETS-family transcription factor PU.1 was required for the development of an interleukin 9 (IL-9)-secreting subset of helper T cells. Decreasing PU.1 expression either by conditional deletion in mouse T cells or the use of small interfering RNA in human T cells impaired IL-9 production, whereas ectopic PU.1 expression promoted IL-9 production. Mice with PU.1-deficient T cells developed normal T helper type 2 (TH2) responses in vivo but showed attenuated allergic pulmonary inflammation that corresponded to lower expression of Il9 and chemokines in peripheral T cells and in lungs than that of wild-type mice. Together our data suggest a critical role for PU.1 in generating the IL-9-producing (TH9) phenotype and in the development of allergic inflammation.
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Acknowledgements
Supported by the National Institutes of Health (R01 AI57459 and U19 AI070448 to M.H.K., R01 CA118118 to M.J.R.; R01 HL080071 to R.S.T.; and T32 AI060519 to G.L.S.).
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M.H.K. designed and supervised the study and wrote the manuscript; H.-C.C., R.G., R.J. and L.H. did experiments in Figures 1,2,3 and Supplementary Figure 1; Q.Y., R.G. and G.L.S. did experiments in Figure 4 and Supplementary Figure 2; W.Y., M.J.R. and R.S.T. obtained human samples; W.Y. did all experiments in Figure 5; S.S., E.T.N., C.M. and A.-N.A. did experiments in Figures 6 and 7 and Supplementary Figure 3; N.B.P. provided bioinformatics analysis; and S.L.N. provided mice.
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Chang, HC., Sehra, S., Goswami, R. et al. The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation. Nat Immunol 11, 527–534 (2010). https://doi.org/10.1038/ni.1867
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DOI: https://doi.org/10.1038/ni.1867
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