Inhibition of Pyruvate Dehydrogenase Kinase 4 in CD4⁺ T Cells Ameliorates Intestinal Inflammation.

ABSTRACT:

Background & aims

Despite recent evidence supporting the metabolic plasticity of CD4⁺ T cells, it is uncertain whether the metabolic checkpoint pyruvate dehydrogenase kinase (PDK) in T cells plays a role in the pathogenesis of colitis.

Methods

To investigate the role of PDK4 in colitis, we used dextran sulfate sodium (DSS)-induced colitis and T-cell transfer colitis models based on mice with constitutive knockout (KO) or CD4⁺ T-cell-specific KO of PDK4 (Pdk4^fl/flCD4^Cre). The effect of PDK4 deletion on T-cell activation was also studied in vitro. Furthermore, we examined the effects of a pharmacologic inhibitor of PDK4 on colitis.

Results

Expression of PDK4 increased during colitis development in a DSS-induced colitis model.

SUBMITTER: Lee H 

PROVIDER: S-EPMC9791136 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature