Human Tolerogenic Dendritic Cells Regulate Immune Responses through Lactate Synthesis.
Cell Metab
; 30(6): 1075-1090.e8, 2019 12 03.
Article
in En
| MEDLINE
| ID: mdl-31801055
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dendritic Cells
/
CD4-Positive T-Lymphocytes
/
Immunosuppression Therapy
/
Lactic Acid
/
Immune Tolerance
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Cell Metab
Journal subject:
METABOLISMO
Year:
2019
Type:
Article
Affiliation country:
France