The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation.
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.
Chang
Hua-Chen
HC
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
Sehra
Sarita
S
Goswami
Ritobrata
R
Yao
Weiguo
W
Yu
Qing
Q
Stritesky
Gretta L
GL
Jabeen
Rukhsana
R
McKinley
Carl
C
Ahyi
Ayele-Nati
AN
Han
Ling
L
Nguyen
Evelyn T
ET
Robertson
Michael J
MJ
Perumal
Narayanan B
NB
Tepper
Robert S
RS
Nutt
Stephen L
SL
Kaplan
Mark H
MH
D000818:Animals; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D006967:Hypersensitivity; D007249:Inflammation; D016906:Interleukin-9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D015534:Trans-Activators / Q000276:immunology*; D000099232:Proto-Oncogene Protein Spi-1
D016906:Interleukin-9; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1