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

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

Research output: Contribution to journalArticle

10 Scopus citations

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 - Jan 1 2015

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Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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