Glutarate regulates T cell function and metabolism
Abstract T cell function is influenced by several metabolites; some acting through enzymatic inhibition of α-KG-dependent dioxygenases (αKGDDs), others, through post-translational modification of lysines in important targets. We show here that glutarate, a product of amino acid catabolism, has the capacity to do both, with effects on T cell function and differentiation. Glutarate exerts those effects through αKGDD inhibition and through direct regulation of T cell metabolism via post-translational modification of the pyruvate dehydrogenase E2 subunit. Diethyl-glutarate, a cell-permeable form of glutarate, alters CD8+T cell differentiation and increases cytotoxicity against target cells.In vivoadministration of the compound reduces tumor growth and is correlated with increased levels of both peripheral and intratumoral cytotoxic CD8+T cells. These results demonstrate that glutarate regulates both T cell metabolism and differentiation, with a potential role in the improvement of T cell immunotherapy..
Medienart: |
Preprint |
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Erscheinungsjahr: |
2022 |
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Erschienen: |
2022 |
Enthalten in: |
bioRxiv.org - (2022) vom: 27. Okt. Zur Gesamtaufnahme - year:2022 |
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Sprache: |
Englisch |
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Beteiligte Personen: |
Minogue, Eleanor [VerfasserIn] |
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Links: |
Volltext [kostenfrei] |
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Themen: |
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doi: |
10.1101/2022.10.20.513065 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
XBI037687867 |
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520 | |a Abstract T cell function is influenced by several metabolites; some acting through enzymatic inhibition of α-KG-dependent dioxygenases (αKGDDs), others, through post-translational modification of lysines in important targets. We show here that glutarate, a product of amino acid catabolism, has the capacity to do both, with effects on T cell function and differentiation. Glutarate exerts those effects through αKGDD inhibition and through direct regulation of T cell metabolism via post-translational modification of the pyruvate dehydrogenase E2 subunit. Diethyl-glutarate, a cell-permeable form of glutarate, alters CD8+T cell differentiation and increases cytotoxicity against target cells.In vivoadministration of the compound reduces tumor growth and is correlated with increased levels of both peripheral and intratumoral cytotoxic CD8+T cells. These results demonstrate that glutarate regulates both T cell metabolism and differentiation, with a potential role in the improvement of T cell immunotherapy. | ||
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700 | 1 | |a Zurita, Javier |e verfasserin |4 aut | |
700 | 1 | |a Teli, Shiv Sah |e verfasserin |4 aut | |
700 | 1 | |a Wadsworth, Brennan J. |e verfasserin |4 aut | |
700 | 1 | |a Hughes, Rob |e verfasserin |4 aut | |
700 | 1 | |a Grice, Guinevere L. |e verfasserin |4 aut | |
700 | 1 | |a Velica, Pedro |e verfasserin |4 aut | |
700 | 1 | |a Bargiela, David |e verfasserin |4 aut | |
700 | 1 | |a Barbieri, Laura |e verfasserin |4 aut | |
700 | 1 | |a Wheelock, Craig E. |e verfasserin |4 aut | |
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700 | 1 | |a Foskolou, Iosifina P. |e verfasserin |4 aut | |
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