Requirement of Mitochondrial Transcription Factor A in Tissue-Resident Regulatory T Cell Maintenance and Function
Summary: Regulatory T cells (Tregs) are pivotal for immune suppression. Cellular metabolism is important for Treg homeostasis and function. However, the exact role of mitochondrial respiration in Tregs remains elusive. Mitochondrial transcription factor A (Tfam) is essential for mitochondrial respir...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-07-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719307909 |
| _version_ | 1818153012183433216 |
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| author | Zheng Fu Jian Ye Joseph W. Dean John W. Bostick Samuel E. Weinberg Lifeng Xiong Kristen N. Oliff Zongming E. Chen Dorina Avram Navdeep S. Chandel Liang Zhou |
| author_facet | Zheng Fu Jian Ye Joseph W. Dean John W. Bostick Samuel E. Weinberg Lifeng Xiong Kristen N. Oliff Zongming E. Chen Dorina Avram Navdeep S. Chandel Liang Zhou |
| author_sort | Zheng Fu |
| collection | DOAJ |
| description | Summary: Regulatory T cells (Tregs) are pivotal for immune suppression. Cellular metabolism is important for Treg homeostasis and function. However, the exact role of mitochondrial respiration in Tregs remains elusive. Mitochondrial transcription factor A (Tfam) is essential for mitochondrial respiration and controls mitochondrial DNA replication, transcription, and packaging. Here, we show that genetic ablation of Tfam in Tregs impairs Treg maintenance in non-lymphoid tissues in the steady state and in tumors. Tfam-deficient Tregs have reduced proliferation and Foxp3 expression upon glucose deprivation in vitro. Tfam deficiency preferentially affects gene activation in Tregs through regulation of DNA methylation, with enhanced methylation in the TSDR of the Foxp3 locus. Deletion of Tfam in Tregs affects Treg homing and stability, resulting in tissue inflammation in colitis, but enhances tumor rejection. Thus, our work reveals a critical role of Tfam-mediated mitochondrial respiration in Tregs to regulate inflammation and anti-tumor immunity. : Cellular metabolism is important for regulatory T cell (Treg) homeostasis and function. Fu et al. show that mitochondrial transcription factor A (Tfam)-mediated mitochondrial respiration is critical for Treg maintenance in non-lymphoid organs and tissues in the steady state and in tumors. Keywords: regulatory T cells, mitochondrial respiration, Tfam, maintenance, tumor |
| first_indexed | 2024-12-11T14:03:50Z |
| format | Article |
| id | doaj.art-276c3dc56b3c4c37a58c0cf7c0a6e7ec |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T14:03:50Z |
| publishDate | 2019-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-276c3dc56b3c4c37a58c0cf7c0a6e7ec2022-12-22T01:03:45ZengElsevierCell Reports2211-12472019-07-01281159171.e4Requirement of Mitochondrial Transcription Factor A in Tissue-Resident Regulatory T Cell Maintenance and FunctionZheng Fu0Jian Ye1Joseph W. Dean2John W. Bostick3Samuel E. Weinberg4Lifeng Xiong5Kristen N. Oliff6Zongming E. Chen7Dorina Avram8Navdeep S. Chandel9Liang Zhou10Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USADepartment of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USADepartment of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USADepartment of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA; Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USADepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USADepartment of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USADepartment of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USAGeisinger Medical Center, Laboratory Medicine, 01-31, 100 North Academy Avenue, Danville, PA 17822, USADepartment of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, FL 32608, USADepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USADepartment of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA; Corresponding authorSummary: Regulatory T cells (Tregs) are pivotal for immune suppression. Cellular metabolism is important for Treg homeostasis and function. However, the exact role of mitochondrial respiration in Tregs remains elusive. Mitochondrial transcription factor A (Tfam) is essential for mitochondrial respiration and controls mitochondrial DNA replication, transcription, and packaging. Here, we show that genetic ablation of Tfam in Tregs impairs Treg maintenance in non-lymphoid tissues in the steady state and in tumors. Tfam-deficient Tregs have reduced proliferation and Foxp3 expression upon glucose deprivation in vitro. Tfam deficiency preferentially affects gene activation in Tregs through regulation of DNA methylation, with enhanced methylation in the TSDR of the Foxp3 locus. Deletion of Tfam in Tregs affects Treg homing and stability, resulting in tissue inflammation in colitis, but enhances tumor rejection. Thus, our work reveals a critical role of Tfam-mediated mitochondrial respiration in Tregs to regulate inflammation and anti-tumor immunity. : Cellular metabolism is important for regulatory T cell (Treg) homeostasis and function. Fu et al. show that mitochondrial transcription factor A (Tfam)-mediated mitochondrial respiration is critical for Treg maintenance in non-lymphoid organs and tissues in the steady state and in tumors. Keywords: regulatory T cells, mitochondrial respiration, Tfam, maintenance, tumorhttp://www.sciencedirect.com/science/article/pii/S2211124719307909 |
| spellingShingle | Zheng Fu Jian Ye Joseph W. Dean John W. Bostick Samuel E. Weinberg Lifeng Xiong Kristen N. Oliff Zongming E. Chen Dorina Avram Navdeep S. Chandel Liang Zhou Requirement of Mitochondrial Transcription Factor A in Tissue-Resident Regulatory T Cell Maintenance and Function Cell Reports |
| title | Requirement of Mitochondrial Transcription Factor A in Tissue-Resident Regulatory T Cell Maintenance and Function |
| title_full | Requirement of Mitochondrial Transcription Factor A in Tissue-Resident Regulatory T Cell Maintenance and Function |
| title_fullStr | Requirement of Mitochondrial Transcription Factor A in Tissue-Resident Regulatory T Cell Maintenance and Function |
| title_full_unstemmed | Requirement of Mitochondrial Transcription Factor A in Tissue-Resident Regulatory T Cell Maintenance and Function |
| title_short | Requirement of Mitochondrial Transcription Factor A in Tissue-Resident Regulatory T Cell Maintenance and Function |
| title_sort | requirement of mitochondrial transcription factor a in tissue resident regulatory t cell maintenance and function |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719307909 |
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