T Cell-Intrinsic Vitamin A Metabolism and Its Signaling Are Targets for Memory T Cell-Based Cancer Immunotherapy
Memory T cells play an essential role in infectious and tumor immunity. Vitamin A metabolites such as retinoic acid are immune modulators, but the role of vitamin A metabolism in memory T-cell differentiation is unclear. In this study, we identified retinol dehydrogenase 10 (Rdh10), which metabolize...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-06-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.935465/full |
| _version_ | 1828195695299919872 |
|---|---|
| author | Fumihiro Fujiki Soyoko Morimoto Akiko Katsuhara Akane Okuda Saeka Ogawa Eriko Ueda Maki Miyazaki Ayako Isotani Ayako Isotani Masahito Ikawa Sumiyuki Nishida Hiroko Nakajima Akihiro Tsuboi Yoshihiro Oka Yoshihiro Oka Yoshihiro Oka Jun Nakata Naoki Hosen Naoki Hosen Atsushi Kumanogoh Atsushi Kumanogoh Yusuke Oji Haruo Sugiyama |
| author_facet | Fumihiro Fujiki Soyoko Morimoto Akiko Katsuhara Akane Okuda Saeka Ogawa Eriko Ueda Maki Miyazaki Ayako Isotani Ayako Isotani Masahito Ikawa Sumiyuki Nishida Hiroko Nakajima Akihiro Tsuboi Yoshihiro Oka Yoshihiro Oka Yoshihiro Oka Jun Nakata Naoki Hosen Naoki Hosen Atsushi Kumanogoh Atsushi Kumanogoh Yusuke Oji Haruo Sugiyama |
| author_sort | Fumihiro Fujiki |
| collection | DOAJ |
| description | Memory T cells play an essential role in infectious and tumor immunity. Vitamin A metabolites such as retinoic acid are immune modulators, but the role of vitamin A metabolism in memory T-cell differentiation is unclear. In this study, we identified retinol dehydrogenase 10 (Rdh10), which metabolizes vitamin A to retinal (RAL), as a key molecule for regulating T cell differentiation. T cell-specific Rdh10 deficiency enhanced memory T-cell formation through blocking RAL production in infection model. Epigenetic profiling revealed that retinoic acid receptor (RAR) signaling activated by vitamin A metabolites induced comprehensive epigenetic repression of memory T cell-associated genes, including TCF7, thereby promoting effector T-cell differentiation. Importantly, memory T cells generated by Rdh deficiency and blocking RAR signaling elicited potent anti-tumor responses in adoptive T-cell transfer setting. Thus, T cell differentiation is regulated by vitamin A metabolism and its signaling, which should be novel targets for memory T cell-based cancer immunotherapy. |
| first_indexed | 2024-04-12T09:47:57Z |
| format | Article |
| id | doaj.art-be408ef12699491a8d81c30d652284b0 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T09:47:57Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-be408ef12699491a8d81c30d652284b02022-12-22T03:37:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.935465935465T Cell-Intrinsic Vitamin A Metabolism and Its Signaling Are Targets for Memory T Cell-Based Cancer ImmunotherapyFumihiro Fujiki0Soyoko Morimoto1Akiko Katsuhara2Akane Okuda3Saeka Ogawa4Eriko Ueda5Maki Miyazaki6Ayako Isotani7Ayako Isotani8Masahito Ikawa9Sumiyuki Nishida10Hiroko Nakajima11Akihiro Tsuboi12Yoshihiro Oka13Yoshihiro Oka14Yoshihiro Oka15Jun Nakata16Naoki Hosen17Naoki Hosen18Atsushi Kumanogoh19Atsushi Kumanogoh20Yusuke Oji21Haruo Sugiyama22Department of Cancer Immunology, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Cancer Stem Cell Biology, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Functional Diagnostic Science, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Functional Diagnostic Science, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Functional Diagnostic Science, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Functional Diagnostic Science, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Functional Diagnostic Science, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita, JapanGraduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, JapanDepartment of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita, JapanDepartment of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Cancer Immunology, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Cancer Immunotherapy, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Cancer Stem Cell Biology, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Immunopathology, WPI Immunology Frontier Research Center, Osaka University, Suita, JapanDepartment of Clinical Laboratory and Biomedical Sciences, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Cancer Stem Cell Biology, Graduate School of Medicine, Osaka University, Suita, Japan0Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Immunopathology, WPI Immunology Frontier Research Center, Osaka University, Suita, JapanDepartment of Clinical Laboratory and Biomedical Sciences, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Cancer Immunology, Graduate School of Medicine, Osaka University, Suita, JapanMemory T cells play an essential role in infectious and tumor immunity. Vitamin A metabolites such as retinoic acid are immune modulators, but the role of vitamin A metabolism in memory T-cell differentiation is unclear. In this study, we identified retinol dehydrogenase 10 (Rdh10), which metabolizes vitamin A to retinal (RAL), as a key molecule for regulating T cell differentiation. T cell-specific Rdh10 deficiency enhanced memory T-cell formation through blocking RAL production in infection model. Epigenetic profiling revealed that retinoic acid receptor (RAR) signaling activated by vitamin A metabolites induced comprehensive epigenetic repression of memory T cell-associated genes, including TCF7, thereby promoting effector T-cell differentiation. Importantly, memory T cells generated by Rdh deficiency and blocking RAR signaling elicited potent anti-tumor responses in adoptive T-cell transfer setting. Thus, T cell differentiation is regulated by vitamin A metabolism and its signaling, which should be novel targets for memory T cell-based cancer immunotherapy.https://www.frontiersin.org/articles/10.3389/fimmu.2022.935465/fullvitamin ARDH10memory T cellretinoic acidcancer immunotherapyvitamin A metabolism |
| spellingShingle | Fumihiro Fujiki Soyoko Morimoto Akiko Katsuhara Akane Okuda Saeka Ogawa Eriko Ueda Maki Miyazaki Ayako Isotani Ayako Isotani Masahito Ikawa Sumiyuki Nishida Hiroko Nakajima Akihiro Tsuboi Yoshihiro Oka Yoshihiro Oka Yoshihiro Oka Jun Nakata Naoki Hosen Naoki Hosen Atsushi Kumanogoh Atsushi Kumanogoh Yusuke Oji Haruo Sugiyama T Cell-Intrinsic Vitamin A Metabolism and Its Signaling Are Targets for Memory T Cell-Based Cancer Immunotherapy Frontiers in Immunology vitamin A RDH10 memory T cell retinoic acid cancer immunotherapy vitamin A metabolism |
| title | T Cell-Intrinsic Vitamin A Metabolism and Its Signaling Are Targets for Memory T Cell-Based Cancer Immunotherapy |
| title_full | T Cell-Intrinsic Vitamin A Metabolism and Its Signaling Are Targets for Memory T Cell-Based Cancer Immunotherapy |
| title_fullStr | T Cell-Intrinsic Vitamin A Metabolism and Its Signaling Are Targets for Memory T Cell-Based Cancer Immunotherapy |
| title_full_unstemmed | T Cell-Intrinsic Vitamin A Metabolism and Its Signaling Are Targets for Memory T Cell-Based Cancer Immunotherapy |
| title_short | T Cell-Intrinsic Vitamin A Metabolism and Its Signaling Are Targets for Memory T Cell-Based Cancer Immunotherapy |
| title_sort | t cell intrinsic vitamin a metabolism and its signaling are targets for memory t cell based cancer immunotherapy |
| topic | vitamin A RDH10 memory T cell retinoic acid cancer immunotherapy vitamin A metabolism |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.935465/full |
| work_keys_str_mv | AT fumihirofujiki tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT soyokomorimoto tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT akikokatsuhara tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT akaneokuda tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT saekaogawa tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT erikoueda tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT makimiyazaki tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT ayakoisotani tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT ayakoisotani tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT masahitoikawa tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT sumiyukinishida tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT hirokonakajima tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT akihirotsuboi tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT yoshihirooka tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT yoshihirooka tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT yoshihirooka tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT junnakata tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT naokihosen tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT naokihosen tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT atsushikumanogoh tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT atsushikumanogoh tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT yusukeoji tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy AT haruosugiyama tcellintrinsicvitaminametabolismanditssignalingaretargetsformemorytcellbasedcancerimmunotherapy |