CD31 regulates metabolic switch in Treg migration attenuates rheumatoid arthritis.

ABSTRACT: CD31 (PECAM-1) plays a critical role in T cell migration, whilst its immunoreceptor tyrosine inhibitory motifs (ITIMs), Y663 and Y686, are recognised for their roles in endothelial function, the precise mechanism in regulating immune cell remains elusive. Here, we demonstrate that CD31 is essential for Treg migration. Upon ITIM engagement, CD31 activates and interacts with the protein tyrosine phosphatase SHP2. In vivo, CD31 Y663F gene transfer recapitulates the wild-type migration phenotype, driven by a metabolic switch to fructose utilisation under the regulation of the PFKFB3 gene. Conversely, the Y686F mutation impairs Tregs migration by disrupting both glycolysis and the switch to fructose metabolism, thus promoting the mitochondrial function via activation of the RNF111/OGT pathway.

SUBMITTER: Liu M 

PROVIDER: S-EPMC12356826 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature