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

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 (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.

• Authors: 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
• Journal: Nature immunology (Nat Immunol) Vol. 11 Issue 6 Pg. 527-34 (Jun 2010) ISSN: 1529-2916 [Electronic] United States
• PMID: 20431622 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Interleukin-9
• Proto-Oncogene Proteins
• Trans-Activators
• proto-oncogene protein Spi-1

Topics

• Animals
• Cell Differentiation
• Female
• Humans
• Hypersensitivity
• Inflammation
• Interleukin-9 (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Proto-Oncogene Proteins (immunology)
• Reverse Transcriptase Polymerase Chain Reaction
• T-Lymphocytes (immunology)
• Trans-Activators (immunology)