Human Tolerogenic Dendritic Cells Regulate Immune Responses through Lactate Synthesis
(2019) Cell Metabolism — Vol. 30, n° 6, p. 1075-1090 (2019)
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- 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 ATDCsecreted 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.
- Affiliations
Université de Nantes 2Centre de Recherche en Cance´ rologie et Immunologie Nantes-Angers UMR1232, INSERM
Citations
Marin, E., Bouchet-Delbos, L., Renoult, O., Louvet, C., Nerriere-Daguin, V., Managh, A. J., Even, A., Giraud, M., Vu Manh, T. P., Aguesse, A., Bériou, G., Chiffoleau, E., Alliot-Licht, B., Prieur, X., Croyal, M., Hutchinson, J. A., Obermajer, N., Geissler, E. K., Vanhove, B., et al. (2019). Human Tolerogenic Dendritic Cells Regulate Immune Responses through Lactate Synthesis. Cell Metabolism, 30(6), 1075-1090. https://doi.org/10.1016/j.cmet.2019.11.011 (Original work published 2019)