| First Author | Papadakis KA | Year | 2015 |
| Journal | Am J Physiol Cell Physiol | Volume | 308 |
| Issue | 5 | Pages | C362-71 |
| PubMed ID | 25472963 | Mgi Jnum | J:223856 |
| Mgi Id | MGI:5660480 | Doi | 10.1152/ajpcell.00262.2014 |
| Citation | Papadakis KA, et al. (2015) Kruppel-like factor KLF10 regulates transforming growth factor receptor II expression and TGF-beta signaling in CD8+ T lymphocytes. Am J Physiol Cell Physiol 308(5):C362-71 |
| abstractText | KLF10 has recently elicited significant attention as a transcriptional regulator of transforming growth factor-beta1 (TGF-beta1) signaling in CD4(+) T cells. In the current study, we demonstrate a novel role for KLF10 in the regulation of TGF-beta receptor II (TGF-betaRII) 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-gamma 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-betaRII (TbetaRII). Congruently, in vitro activation of KLF10-deficient CD8(+) T cells upregulate TGF-betaRII to a lesser extent compared with wild-type (WT) CD8(+) T cells, which results in attenuated Smad2 phosphorylation following TGF-beta1 stimulation compared with WT CD8(+) T cells. Moreover, we demonstrate that KLF10 directly binds to the TGF-betaRII 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-betaRII among viral-specific KLF10(-/-) CD8(+) T cells and a higher percentage of IFN-gamma-producing CD8(+) T cells in the spleen. Collectively, our data reveal a critical role for KLF10 in the transcriptional activation of TGF-betaRII in CD8(+) T cells. Thus, KLF10 regulation of TGF-betaRII in this cell subset may likely play a critical role in viral and tumor immune responses for which the integrity of the TGF-beta1/TGF-betaRII signaling pathway is crucial. |
