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

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, Michael J. Robertson, Narayanan B. Perumal, Robert S. Tepper, Stephen L. Nutt, Mark H. Kaplan

Research output: Contribution to journalArticle

370 Scopus citations

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 (TH 2) 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 (TH 9) phenotype and in the development of allergic inflammation.

Original languageEnglish (US)
Pages (from-to)527-534
Number of pages8
JournalNature Immunology
Volume11
Issue number6
DOIs
StatePublished - Jun 1 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Chang, H. C., Sehra, S., Goswami, R., Yao, W., Yu, Q., Stritesky, G. L., Jabeen, R., McKinley, C., Ahyi, A. N., Han, L., Nguyen, E. T., Robertson, M. J., Perumal, N. B., Tepper, R. S., Nutt, S. L., & Kaplan, M. H. (2010). The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation. Nature Immunology, 11(6), 527-534. https://doi.org/10.1038/ni.1867