Marin, Eros and Bouchet-Delbos, Laurence and Renoult, Ophelie and Louvet, Cedric and Nerriere-Daguin, Veronique and Managh, Amy J. and Even, Amandine and Giraud, Matthieu and Thien Phong Vu Manh, and Aguesse, Audrey and Beriou, Gaelle and Chiffoleau, Elise and Alliot-Licht, Brigitte and Prieur, Xavier and Croyal, Mikael and Hutchinson, James A. and Obermajer, Natasa and Geissler, Edward K. and Vanhove, Bernard and Blancho, Gilles and Dalod, Marc and Josien, Regis and Pecqueur, Claire and Cuturi, Maria-Cristina and Moreau, Aurelie (2019) Human Tolerogenic Dendritic Cells Regulate Immune Responses through Lactate Synthesis. CELL METABOLISM, 30 (6). 1075-+. ISSN 1550-4131, 1932-7420
Full text not available from this repository. (Request a copy)Abstract
Cell therapy is a promising strategy for treating patients suffering from autoimmune or inflammatory diseases or receiving a transplant. Based on our preclinical studies, we have generated human autologous tolerogenic dendritic cells (ATDCs), which are being tested in a first-in-man clinical trial in kidney transplant recipients. Here, we report that ATDCs represent a unique subset of monocyte-derived cells based on phenotypic, transcriptomic, and metabolic analyses. ATDCs are characterized by their suppression of T cell proliferation and their expansion of Tregs through secreted factors. ATDCs produce high levels of lactate that shape T cell responses toward tolerance. Indeed, T cells take up ATDC-secreted lactate, leading to a decrease of their glycolysis. In vivo, ATDCs promote elevated levels of circulating lactate and delay graft-versus-host disease by reducing T cell proliferative capacity. The suppression of T cell immunity through lactate production by ATDCs is a novel mechanism that distinguishes ATDCs from other cell-based immunotherapies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROLONG ALLOGRAFT SURVIVAL; CD4(+) T-CELLS; LACTIC-ACID; MACROPHAGES; MOUSE; METABOLISM; ACTIVATION; EXPRESSION; RECEPTOR; THERAPY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Mar 2020 09:39 |
| Last Modified: | 20 Mar 2020 09:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25696 |
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