2134/11310755.v1
Eros Marin
Eros
Marin
Laurence Bouchet-Delbos
Laurence
Bouchet-Delbos
Ophélie Renoult
Ophélie
Renoult
Cédric Louvet
Cédric
Louvet
Véronique Nerriere-Daguin
Véronique
Nerriere-Daguin
Amy Managh
Amy
Managh
Amandine Even
Amandine
Even
Matthieu Giraud
Matthieu
Giraud
Thien Phong Vu Manh
Thien Phong Vu
Manh
Audrey Aguesse
Audrey
Aguesse
Gaelle Bériou
Gaelle
Bériou
Elise Chiffoleau
Elise
Chiffoleau
Brigitte Alliot-Licht
Brigitte
Alliot-Licht
Xavier Prieur
Xavier
Prieur
Mikael Croyal
Mikael
Croyal
James A Hutchinson
James A
Hutchinson
Natasa Obermajer
Natasa
Obermajer
Edward K Geissler
Edward K
Geissler
Bernard Vanhove
Bernard
Vanhove
Gilles Blancho
Gilles
Blancho
Marc Dalod
Marc
Dalod
Régis Josien
Régis
Josien
Claire Pecqueur
Claire
Pecqueur
Maria-Cristina Cuturi
Maria-Cristina
Cuturi
Aurélie Moreau
Aurélie
Moreau
Human tolerogenic dendritic cells regulate immune responses through lactate synthesis
Loughborough University
2019
Lactate
Immunometabolism
Tolerance induction
Tolerogenic dendritic cells
Cell therapy in humans
2019-12-04 14:08:02
Journal contribution
https://repository.lboro.ac.uk/articles/journal_contribution/Human_tolerogenic_dendritic_cells_regulate_immune_responses_through_lactate_synthesis/11310755
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.