| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Papadakis, Konstantinos A. Krempski, James Reiter, Jesse Svingen, Phyllis Xiong, Yuning Sarmento, Olga F. Huseby, April Johnson, Aaron J. Lomberk, Gwen A. Urrutia, Raul A. Faubion, William A. |
| Description |
Author Affiliation: Papadakis KA ( Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota); Krempski J ( Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota); Reiter J ( Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota); Svingen P ( Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota); Xiong Y ( Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota); Sarmento OF ( Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota); Huseby A ( Division of Immunology and Neurology, Mayo Clinic, Rochester, Minnesota); Johnson AJ ( Division of Immunology and Neurology, Mayo Clinic, Rochester, Minnesota); Lomberk GA ( Epigenetics and Chromatin Dynamics Laboratory, Departments of Medicine and Biochemistry and Molecular Biology, Epigenetic Translational Program, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota.); Urrutia RA ( Epigenetics and Chromatin Dynamics Laboratory, Departments of Medicine and Biochemistry and Molecular Biology, Epigenetic Translational Program, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota.); Faubion WA ( Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota) |
| Abstract |
KLF10 has recently elicited significant attention as a transcriptional regulator of transforming growth factor-ß1 (TGF-ß1) signaling in CD4(+) T cells. In the current study, we demonstrate a novel role for KLF10 in the regulation of TGF-ß receptor II (TGF-ßRII) 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-ßRII (TßRII). Congruently, in vitro activation of KLF10-deficient CD8(+) T cells upregulate TGF-ßRII to a lesser extent compared with wild-type (WT) CD8(+) T cells, which results in attenuated Smad2 phosphorylation following TGF-ß1 stimulation compared with WT CD8(+) T cells. Moreover, we demonstrate that KLF10 directly binds to the TGF-ßRII 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-ßRII 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-ßRII in CD8(+) T cells. Thus, KLF10 regulation of TGF-ßRII in this cell subset may likely play a critical role in viral and tumor immune responses for which the integrity of the TGF-ß1/TGF-ßRII signaling pathway is crucial. |
| File Format |
HTM / HTML |
| ISSN |
03636143 |
| e-ISSN |
15221563 |
| DOI |
10.1152/ajpcell.00262.2014 |
| Journal |
American Journal of Physiology - Cell Physiology |
| Issue Number |
5 |
| Volume Number |
308 |
| Language |
English |
| Publisher |
American Physiological Society |
| Publisher Date |
2015-03-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Discipline Cell Biology Cd8-positive T-lymphocytes Metabolism Early Growth Response Transcription Factors Physiology Kruppel-like Transcription Factors Protein-serine-threonine Kinases Biosynthesis Receptors, Transforming Growth Factor Beta Transforming Growth Factor Beta Animals Cells, Cultured Deficiency Gene Expression Regulation Jurkat Cells Mice Mice, Inbred Balb C Mice, Inbred C57bl Mice, Knockout Mice, Transgenic Research Support, N.i.h., Extramural |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Cell Biology Physiology |
