Reference - Detail
| RRC ID | 81251 |
|---|---|
| Author | Fujiki F, Morimoto S, Katsuhara A, Okuda A, Ogawa S, Ueda E, Miyazaki M, Isotani A, Ikawa M, Nishida S, Nakajima H, Tsuboi A, Oka Y, Nakata J, Hosen N, Kumanogoh A, Oji Y, Sugiyama H. |
| Title | T Cell-Intrinsic Vitamin A Metabolism and Its Signaling Are Targets for Memory T Cell-Based Cancer Immunotherapy. |
| Journal | Front Immunol |
| Abstract |
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. |
| Volume | 13 |
| Pages | 935465 |
| Published | 2022-1-1 |
| DOI | 10.3389/fimmu.2022.935465 |
| PMID | 35844620 |
| PMC | PMC9280205 |
| MeSH | Alcohol Oxidoreductases / genetics Alcohol Oxidoreductases / metabolism Immunotherapy Memory T Cells Neoplasms* / therapy Tretinoin / pharmacology Vitamin A* / metabolism |
| IF | 5.085 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| DNA material | CSII-EF-MCS-IRES2-Venus (RDB04384) CS-RfA-EG (RDB04391) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |