Krüppel-like factor KLF10 regulates transforming growth factor receptor II expression and TGF-β signaling in CD8+ T lymphocytes

Konstantinos Papadakis, James Krempski, Jesse Reiter, Phyllis Svingen, Yuning Xiong, Olga F. Sarmento, April Huseby, Aaron J. Johnson, Gwen A. Lomberk, Raul A. Urrutia, William Alvis Faubion

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)C362-C371
JournalAmerican Journal of Physiology - Cell Physiology
Volume308
Issue number5
DOIs
StatePublished - 2015

Fingerprint

Growth Factor Receptors
Transforming Growth Factors
T-Lymphocytes
Spleen
Theilovirus
Th1 Cells
Virus Diseases
Transcriptional Activation
Antiviral Agents
Up-Regulation
Phosphorylation
Gene Expression

Keywords

  • KLF10
  • Krüppel-like factor
  • T regulatory cell
  • TGF-β receptor II

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

Cite this

Krüppel-like factor KLF10 regulates transforming growth factor receptor II expression and TGF-β signaling in CD8+ T lymphocytes. / Papadakis, Konstantinos; Krempski, James; Reiter, Jesse; Svingen, Phyllis; Xiong, Yuning; Sarmento, Olga F.; Huseby, April; Johnson, Aaron J.; Lomberk, Gwen A.; Urrutia, Raul A.; Faubion, William Alvis.

In: American Journal of Physiology - Cell Physiology, Vol. 308, No. 5, 2015, p. C362-C371.

Research output: Contribution to journalArticle

Papadakis, Konstantinos ; Krempski, James ; Reiter, Jesse ; Svingen, Phyllis ; Xiong, Yuning ; Sarmento, Olga F. ; Huseby, April ; Johnson, Aaron J. ; Lomberk, Gwen A. ; Urrutia, Raul A. ; Faubion, William Alvis. / Krüppel-like factor KLF10 regulates transforming growth factor receptor II expression and TGF-β signaling in CD8+ T lymphocytes. In: American Journal of Physiology - Cell Physiology. 2015 ; Vol. 308, No. 5. pp. C362-C371.
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AU - Reiter, Jesse

AU - Svingen, Phyllis

AU - Xiong, Yuning

AU - Sarmento, Olga F.

AU - Huseby, April

AU - Johnson, Aaron J.

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AU - Urrutia, Raul A.

AU - Faubion, William Alvis

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