Kruppel-like transcription factor 13 regulates T lymphocyte survival in vivo

M Zhou, L McPherson, D Feng, A Song… - The Journal of …, 2007 - journals.aai.org
M Zhou, L McPherson, D Feng, A Song, C Dong, SC Lyu, L Zhou, X Shi, YT Ahn, D Wang
The Journal of Immunology, 2007journals.aai.org
Krüppel-like transcription factor (KLF) 13, previously shown to regulate RANTES
expression in vitro, is a member of the Krüppel-like family of transcription factors that
controls many growth and developmental processes. To ascertain the function of KLF13 in
vivo, Klf13-deficient mice were generated by gene targeting. As expected, activated T
lymphocytes from Klf13−/− mice show decreased RANTES expression. However, these mice
also exhibit enlarged thymi and spleens. TUNEL, as well as spontaneous and activation …
Abstract
Krüppel-like transcription factor (KLF) 13, previously shown to regulate RANTES expression in vitro, is a member of the Krüppel-like family of transcription factors that controls many growth and developmental processes. To ascertain the function of KLF13 in vivo, Klf13-deficient mice were generated by gene targeting. As expected, activated T lymphocytes from Klf13−/− mice show decreased RANTES expression. However, these mice also exhibit enlarged thymi and spleens. TUNEL, as well as spontaneous and activation-induced death assays, demonstrated that prolonged survival of Klf13−/− thymocytes was due to decreased apoptosis. Microarray analysis suggests that protection from apoptosis-inducing stimuli in Klf13−/− thymocytes is due in part to increased expression of BCL-X L, a potent antiapoptotic factor. This finding was confirmed in splenocytes and total thymocytes by real-time quantitative PCR and Western blot as well as in CD4+ CD8− single-positive thymocytes by real-time quantitative PCR. Furthermore, EMSA and luciferase reporter assays demonstrated that KLF13 binds to multiple sites within the Bcl-X L promoter and results in decreased Bcl-X L promoter activity, making KLF13 a negative regulator of BCL-X L.
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