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The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation

Nature Immunology volume 11, pages 527–534 (2010)Cite this article

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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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Figure 1: PU.1 is required for optimal IL-9 production in mouse T cells.
Figure 2: PU.1 promotes IL-9 production.
Figure 3: IL-9 and IL-10 are not coordinately regulated in TH9 cells.
Figure 4: Histone modifications at the Il9 locus.
Figure 5: PU.1 promotes IL-9 production in human T cells.
Figure 6: PU.1 expression in T cells is required for the development of allergic inflammation.
Figure 7: PU.1 is required for the expression of IL-9 and chemokines in allergen-sensitized mice.

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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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Author notes

  1. Hua-Chen Chang and Sarita Sehra: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA

    Hua-Chen Chang, Sarita Sehra, Ritobrata Goswami, Weiguo Yao, Qing Yu, Gretta L Stritesky, Rukhsana Jabeen, Carl McKinley, Ayele-Nati Ahyi, Ling Han, Evelyn T Nguyen, Robert S Tepper & Mark H Kaplan

  2. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA

    Ritobrata Goswami, Gretta L Stritesky, Ayele-Nati Ahyi & Mark H Kaplan

  3. Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA

    Michael J Robertson

  4. School of Informatics, Indiana University-Purdue University, Indianapolis, Indianapolis, Indiana, USA

    Narayanan B Perumal

  5. The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia

    Stephen L Nutt

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Contributions

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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Correspondence to Mark H Kaplan.

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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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