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Human Tolerogenic Dendritic Cells Regulate Immune Responses through Lactate Synthesis

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.
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Submitted on : Thursday, November 19, 2020 - 9:20:27 AM
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Eros Marín, Laurence Bouchet-Delbos, Ophélie Renoult, Cédric Louvet, Véronique Nerriere-Daguin, et al.. Human Tolerogenic Dendritic Cells Regulate Immune Responses through Lactate Synthesis. Cell Metabolism, Elsevier, 2019, 30 (6), pp.1075-1090. ⟨10.1016/j.cmet.2019.11.011⟩. ⟨inserm-03013619⟩



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