Krüppel-like factor KLF10 regulates transforming growth factor receptor II expression and TGF-β signaling in CD8+ T lymphocytes. Am J Physiol Cell Physiol 2015 Mar 01;308(5):C362-71
Date
12/05/2014Pubmed ID
25472963Pubmed Central ID
PMC4346734DOI
10.1152/ajpcell.00262.2014Scopus ID
2-s2.0-84923870639 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
KLF10 has recently elicited significant attention as a transcriptional regulator of transforming growth factor-β1 (TGF-β1) signaling in CD4(+) T cells. In the current study, we demonstrate a novel role for KLF10 in the regulation of TGF-β receptor II (TGF-βRII) expression with functional relevance in antiviral immune response. Specifically, we show that KLF10-deficient mice have an increased number of effector/memory CD8(+) T cells, display higher levels of the T helper type 1 cell-associated transcription factor T-bet, and produce more IFN-γ following in vitro stimulation. In addition, KLF10(-/-) CD8(+) T cells show enhanced proliferation in vitro and homeostatic proliferation in vivo. Freshly isolated CD8(+) T cells from the spleen of adult mice express lower levels of surface TGF-βRII (TβRII). Congruently, in vitro activation of KLF10-deficient CD8(+) T cells upregulate TGF-βRII to a lesser extent compared with wild-type (WT) CD8(+) T cells, which results in attenuated Smad2 phosphorylation following TGF-β1 stimulation compared with WT CD8(+) T cells. Moreover, we demonstrate that KLF10 directly binds to the TGF-βRII promoter in T cells, leading to enhanced gene expression. In vivo viral infection with Daniel's strain Theiler's murine encephalomyelitis virus (TMEV) also led to lower expression of TGF-βRII among viral-specific KLF10(-/-) CD8(+) T cells and a higher percentage of IFN-γ-producing CD8(+) T cells in the spleen. Collectively, our data reveal a critical role for KLF10 in the transcriptional activation of TGF-βRII in CD8(+) T cells. Thus, KLF10 regulation of TGF-βRII in this cell subset may likely play a critical role in viral and tumor immune responses for which the integrity of the TGF-β1/TGF-βRII signaling pathway is crucial.
Author List
Papadakis KA, Krempski J, Reiter J, Svingen P, Xiong Y, Sarmento OF, Huseby A, Johnson AJ, Lomberk GA, Urrutia RA, Faubion WAAuthor
Gwen Lomberk PhD Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCD8-Positive T-Lymphocytes
Cells, Cultured
Early Growth Response Transcription Factors
Gene Expression Regulation
Humans
Jurkat Cells
Kruppel-Like Transcription Factors
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Receptors, Transforming Growth Factor beta
Transforming Growth Factor beta
