Metabolic signature and proteasome activity controls synovial migration of CDC42^hiCD14⁺ cells in rheumatoid arthritis.

ABSTRACT:

Objective

Activation of Rho-GTPases in macrophages causes inflammation and severe arthritis in mice. In this study, we explore if Rho-GTPases define the joint destination of pathogenic leukocytes, the mechanism by which they perpetuate rheumatoid arthritis (RA), and how JAK inhibition mitigates these effects.

Methods

CD14⁺ cells of 136 RA patients were characterized by RNA sequencing and cytokine measurement to identify biological processes and transcriptional regulators specific for CDC42 ^hiCD14⁺ cells, which were summarized in a metabolic signature (MetSig). The effect of hypoxia and IFN-γ signaling on the metabolic signature of CD14⁺ cells was assessed experimentally. To investigate its connection with joint inflammation,

SUBMITTER: Malmhall-Bah E 

PROVIDER: S-EPMC10469903 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature