Intracellular metabolic adaptation of intraepithelial CD4+CD8αα+ T lymphocytes
Summary: Intestinal intraepithelial lymphocytes (IELs), the first line of defense against microbial and dietary antigens, are classified as natural or induced based on their origin and receptor expression. Induced CD4+CD8αα+TCRβ+ T cells (double positive, DPIELs) originated from CD4+CD8α−TCRβ+ T cel...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-04-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222002917 |
| _version_ | 1819079037493968896 |
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| author | Yosuke Harada Tomohisa Sujino Kentaro Miyamoto Ena Nomura Yusuke Yoshimatsu Shun Tanemoto Satoko Umeda Keiko Ono Yohei Mikami Nobuhiro Nakamoto Kaoru Takabayashi Naoki Hosoe Haruhiko Ogata Tuneo Ikenoue Atsushi Hirao Yoshiaki Kubota Takanori Kanai |
| author_facet | Yosuke Harada Tomohisa Sujino Kentaro Miyamoto Ena Nomura Yusuke Yoshimatsu Shun Tanemoto Satoko Umeda Keiko Ono Yohei Mikami Nobuhiro Nakamoto Kaoru Takabayashi Naoki Hosoe Haruhiko Ogata Tuneo Ikenoue Atsushi Hirao Yoshiaki Kubota Takanori Kanai |
| author_sort | Yosuke Harada |
| collection | DOAJ |
| description | Summary: Intestinal intraepithelial lymphocytes (IELs), the first line of defense against microbial and dietary antigens, are classified as natural or induced based on their origin and receptor expression. Induced CD4+CD8αα+TCRβ+ T cells (double positive, DPIELs) originated from CD4+CD8α−TCRβ+ T cells (single positive, SPIELs) increase with aging. However, the metabolic requirements and the metabolic-related genes in IEL development remain unclear. We determined that the intraepithelial compartment is hypoxic in the presence of microbes and DPIELs increased more than natural IELs in this location. Moreover, DPIELs consumed less oxygen and glucose and exhibited unique alterations in mitochondria. Using inhibitors and genetically modified mice, we revealed that DPIELs adapt to their surrounding oxygen-deprived environment in peripheral tissues by modulating specific genes, including hypoxia-inducible factor, mammalian target of rapamycin complexes (mTORC), phosphorylated ribosomal protein S6 (pS6), and other glycolytic factors. Our findings provide valuable insight into the metabolic properties of IELs. |
| first_indexed | 2024-12-21T19:22:37Z |
| format | Article |
| id | doaj.art-0603827265af48c8be951c4f33903cb5 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-21T19:22:37Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-0603827265af48c8be951c4f33903cb52022-12-21T18:52:54ZengElsevieriScience2589-00422022-04-01254104021Intracellular metabolic adaptation of intraepithelial CD4+CD8αα+ T lymphocytesYosuke Harada0Tomohisa Sujino1Kentaro Miyamoto2Ena Nomura3Yusuke Yoshimatsu4Shun Tanemoto5Satoko Umeda6Keiko Ono7Yohei Mikami8Nobuhiro Nakamoto9Kaoru Takabayashi10Naoki Hosoe11Haruhiko Ogata12Tuneo Ikenoue13Atsushi Hirao14Yoshiaki Kubota15Takanori Kanai16Department of Gastroenterology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanCenter for Diagnostic and Therapeutic Endoscopy, Keio University Hospital, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; Corresponding authorDepartment of Gastroenterology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; Miyarisan Pharmaceutical Co. Ltd. Tokyo 114-0016, JapanDepartment of Gastroenterology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDepartment of Gastroenterology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDepartment of Gastroenterology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDepartment of Gastroenterology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDepartment of Gastroenterology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDepartment of Gastroenterology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDepartment of Gastroenterology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanCenter for Diagnostic and Therapeutic Endoscopy, Keio University Hospital, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanCenter for Diagnostic and Therapeutic Endoscopy, Keio University Hospital, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanCenter for Diagnostic and Therapeutic Endoscopy, Keio University Hospital, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDivision of Clinical Genome Research, The Institute of Medical Science, The University of Tokyo, Tokyo, JapanDivision of Molecular Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, JapanDepartment of Anatomy, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Gastroenterology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; Corresponding authorSummary: Intestinal intraepithelial lymphocytes (IELs), the first line of defense against microbial and dietary antigens, are classified as natural or induced based on their origin and receptor expression. Induced CD4+CD8αα+TCRβ+ T cells (double positive, DPIELs) originated from CD4+CD8α−TCRβ+ T cells (single positive, SPIELs) increase with aging. However, the metabolic requirements and the metabolic-related genes in IEL development remain unclear. We determined that the intraepithelial compartment is hypoxic in the presence of microbes and DPIELs increased more than natural IELs in this location. Moreover, DPIELs consumed less oxygen and glucose and exhibited unique alterations in mitochondria. Using inhibitors and genetically modified mice, we revealed that DPIELs adapt to their surrounding oxygen-deprived environment in peripheral tissues by modulating specific genes, including hypoxia-inducible factor, mammalian target of rapamycin complexes (mTORC), phosphorylated ribosomal protein S6 (pS6), and other glycolytic factors. Our findings provide valuable insight into the metabolic properties of IELs.http://www.sciencedirect.com/science/article/pii/S2589004222002917Biological sciencesImmunologyComponents of the immune systemCell biology |
| spellingShingle | Yosuke Harada Tomohisa Sujino Kentaro Miyamoto Ena Nomura Yusuke Yoshimatsu Shun Tanemoto Satoko Umeda Keiko Ono Yohei Mikami Nobuhiro Nakamoto Kaoru Takabayashi Naoki Hosoe Haruhiko Ogata Tuneo Ikenoue Atsushi Hirao Yoshiaki Kubota Takanori Kanai Intracellular metabolic adaptation of intraepithelial CD4+CD8αα+ T lymphocytes iScience Biological sciences Immunology Components of the immune system Cell biology |
| title | Intracellular metabolic adaptation of intraepithelial CD4+CD8αα+ T lymphocytes |
| title_full | Intracellular metabolic adaptation of intraepithelial CD4+CD8αα+ T lymphocytes |
| title_fullStr | Intracellular metabolic adaptation of intraepithelial CD4+CD8αα+ T lymphocytes |
| title_full_unstemmed | Intracellular metabolic adaptation of intraepithelial CD4+CD8αα+ T lymphocytes |
| title_short | Intracellular metabolic adaptation of intraepithelial CD4+CD8αα+ T lymphocytes |
| title_sort | intracellular metabolic adaptation of intraepithelial cd4 cd8αα t lymphocytes |
| topic | Biological sciences Immunology Components of the immune system Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222002917 |
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