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Journal articles
Human Tolerogenic Dendritic Cells Regulate Immune Responses through Lactate Synthesis
Eros Marín
1
Laurence Bouchet-Delbos
1
Ophélie Renoult
2
Cédric Louvet
1
Véronique Nerriere-Daguin
1, 3, 4
Amy Managh
5
Amandine Even
1
Matthieu Giraud
1
Thien-Phong Vu Manh
6
Audrey Aguesse
7
Gaëlle Bériou
1
Elise Chiffoleau
1
Brigitte Alliot-Licht
1, 4, 8
Xavier Prieur
9
Mickael Croyal
7
James Hutchinson
10
Natasa Obermajer
11
Edward Geissler
10
Bernard Vanhove
1, 3
Gilles Blancho
1
Marc Dalod
6
Régis Josien
4, 1
Claire Pecqueur
3, 2
Maria-Christina Cuturi
1
Aurélie Moreau
3, 1, 4, *
*
Corresponding author
2
CRCINA-ÉQUIPE 14 - Endothelium Radiobiology and Targeting
CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
Eros Marín 1
Author
Laurence Bouchet-Delbos 1
Author
Ophélie Renoult 2
Author
Cédric Louvet 1
Author
Véronique Nerriere-Daguin 1, 3, 4
Author
Amy Managh 5
Author
Amandine Even 1
Author
Matthieu Giraud 1
Author
Thien-Phong Vu Manh 6
Author IdHAL : thien-phong-vu-manh ORCID : https://orcid.org/0000-0002-0294-342X
Audrey Aguesse 7
Author
Gaëlle Bériou 1
Author
Elise Chiffoleau 1
Author
Brigitte Alliot-Licht 1, 4, 8
Author
Xavier Prieur 9
Author
Mickael Croyal 7
Author
James A Hutchinson 10
Author
Natasa Obermajer 11
Author
Edward K. Geissler 10
Author
Bernard Vanhove 1, 3
Author
Gilles Blancho 1
Author
Marc Dalod 6
Author IdHAL : marc-dalod
Régis Josien 4, 1
Author
Claire Pecqueur 3, 2
Author IdHAL : clairepecqueur ORCID : https://orcid.org/0000-0002-7612-1672
Maria-Christina Cuturi 1
Author
Aurélie Moreau 3, 1, 4
Correspondent author
1
U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie (CHU Nantes - Hôtel Dieu - 30 Bd Jean Monnet 44093 Nantes Cedex 01. - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1064 (101, rue de Tolbiac, 75013 Paris - France)
- UFR MEDECINE - Université de Nantes - UFR de Médecine et des Techniques Médicales (1 rue Gaston Veil BP 53508 44035 NANTES Cedex 1 - France)
- UN - Université de Nantes (1, quai de Tourville - BP 13522 - 44035 Nantes cedex 1 - France)
2
CRCINA-ÉQUIPE 14 - Endothelium Radiobiology and Targeting (Institut de Recherche en Santé de l'Université de Nantes - 8 quai Moncousu - BP 70721 - 44007 Nantes cedex 1 - France)
- CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (8 quai de Moncousu - BP 70721 - 44007 Nantes Cedex 1 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : UMR1232 (101, rue de Tolbiac, 75013 Paris - France)
- UFR MEDECINE - Université de Nantes - UFR de Médecine et des Techniques Médicales : UMR1232 (1 rue Gaston Veil BP 53508 44035 NANTES Cedex 1 - France)
- UN - Université de Nantes (1, quai de Tourville - BP 13522 - 44035 Nantes cedex 1 - France)
- CHU Nantes - Centre hospitalier universitaire de Nantes : UMR1232 (1 Place Alexis-Ricordeau, 44000 Nantes - France)
- CNRS - Centre National de la Recherche Scientifique : ERL6001 (France)
- UA - Université d'Angers : UMR1232 (Université d'Angers - 40 Rue de Rennes, BP 73532 - 49035 Angers CEDEX 01 - France)
3
LabEX IGO Immunothérapie Grand Ouest (France)
4
ITUN - Institut de transplantation urologie-néphrologie (France)
- UN - Université de Nantes (1, quai de Tourville - BP 13522 - 44035 Nantes cedex 1 - France)
- CHU Nantes - Centre hospitalier universitaire de Nantes (1 Place Alexis-Ricordeau, 44000 Nantes - France)
5
Loughborough University (Epinal Way, Loughborough, Leicestershire, UK, LE11 3TU - United Kingdom)
6
CIML - Centre d'Immunologie de Marseille - Luminy (Parc scientifique et technologique de Luminy - 163, avenue de Luminy - Case 906 - 13288 Marseille cedex 09 - France)
- AMU - Aix Marseille Université : UM 2 (Aix-Marseille Université Jardins du Pharo 58 Boulevard Charles Livon 13284 Marseille cedex 7 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : UMR_S 1104 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMR7280 (France)
7
PhAN - Physiologie des Adaptations Nutritionnelles [UMR_A1280] (1 place Alexis Ricordeau 44093 Nantes Cedex 1 France - France)
- INRA - Institut National de la Recherche Agronomique : UMR_A1280 (France)
- UN - Université de Nantes (1, quai de Tourville - BP 13522 - 44035 Nantes cedex 1 - France)
8
Faculté d'odontologie [Nancy] (96 avenue Maréchal de Lattre de Tassigny, BP 50208, 54004 NANCY CEDEX - France)
- UL - Université de Lorraine (34 cours Léopold - CS 25233 - 54052 Nancy cedex - France)
9
ITX - unité de recherche de l'institut du thorax UMR1087 UMR6291 (8 quai Moncousu - BP 70721 - 44007 Nantes Cedex 1 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1087 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMR6291 (France)
- UFR MEDECINE - Université de Nantes - UFR de Médecine et des Techniques Médicales (1 rue Gaston Veil BP 53508 44035 NANTES Cedex 1 - France)
- UN - Université de Nantes (1, quai de Tourville - BP 13522 - 44035 Nantes cedex 1 - France)
10
University Hospital Regensburg (Franz-Josef-Strauß-Allee 11, 93053 Regensburg - Germany)
11
PITT - University of Pittsburgh (4200 Fifth Avenue Pittsburgh, PA 15260 - United States)
- Pennsylvania Commonwealth System of Higher Education (PCSHE) (United States)
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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Journal articles
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https://www.hal.inserm.fr/inserm-03013619
Contributor : Elizabeth Bernardo <>
Submitted on : Thursday, November 19, 2020 - 9:20:27 AM
Last modification on : Thursday, February 18, 2021 - 2:18:50 PM
Long-term archiving on: : Saturday, February 20, 2021 - 6:26:12 PM
Contributor : Elizabeth Bernardo <>
Submitted on : Thursday, November 19, 2020 - 9:20:27 AM
Last modification on : Thursday, February 18, 2021 - 2:18:50 PM
Long-term archiving on: : Saturday, February 20, 2021 - 6:26:12 PM
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Distributed under a Creative Commons Attribution - NoDerivatives 4.0 International License
Identifiers
- HAL Id : inserm-03013619, version 1
- DOI : 10.1016/j.cmet.2019.11.011
- PUBMED : 31801055
- WOS : 000500800300009
Collections
INSERM | UNIV-LORRAINE | CRCINA | UNIV-NANTES | THORAX-UMR | CRTI | UNIV-AMU | UNIV-ANGERS | CNRS | INRAE | INRA
Citation
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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