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


Chang, HC; Sehra, S; Goswami, R; Yao, WG; Yu, Q; Stritesky, GL; Jabeen, R; McKinley, C; Ahyi, AN; Han, L; Nguyen, ET; Robertson, MJ; Perumal, NB; Tepper, RS; Nutt, SL; Kaplan, MH
2010-06
NATURE IMMUNOLOGY
Journal Article
11
6
527-U98
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 (T(H)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 (T(H)9) phenotype and in the development of allergic inflammation.
NATURE PUBLISHING GROUP
AIRWAY INFLAMMATION; FATE DETERMINATION; EPITHELIAL-CELLS; TGF-BETA; IL-9; EXPRESSION; ASTHMA; DIFFERENTIATION; LINEAGE; HYPERREACTIVITY
10.1038/ni.1867
Refer to copyright notice on published article.

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Creation Date 2010-06-01 12:00:00