Rheumatoid arthritis synovial microenvironment induces metabolic and functional adaptations in dendritic cells.

Rheumatoid arthritis synovial microenvironment induces metabolic and functional adaptations in dendritic cells. Clin Exp Immunol. 2020 Jun 17;: Authors: Canavan M, Marzaioli V, McGarry T, Bhargava V, Nagpal S, Veale DJ, Fearon U Abstract Rheumatoid Arthritis (RA) is a chronic autoimmune disease which causes degradation of cartilage and bone. It is well appreciated that the pathogenic hallmark of RA is the mass influx of inflammatory cells into the joint. However, the role dendritic cells (DC) may play in this inflammatory milieu is still relatively unexplored. Moreover, the contribution this unique synovial microenvironment has on DC maturation is still unknown. Using monocyte-derived DC (MoDC), we established an in vitro model to recapitulate the synovial microenvironment to explore DC maturation. MoDC treated with conditioned media from ex vivo synovial tissue biopsy cultures (ECM) have increased expression of proinflammatory cytokines, chemokines and adhesion molecules. ECM DC have increased expression of CD83 and CCR7 and decreased expression of CCR5 and phagocytic capacity, suggestive of heightened DC maturation. ECM induced maturation is concomitant with altered cellular bioenergetics, whereby increased expression of glycolytic genes and increased glucose uptake are observed in ECM DC. Collectively, this results in a metabolic shift in DC metabolism in favor of glycolysis. These adaptations are in-part mediated via STAT3 as dem...
Source: Clinical and Developmental Immunology - Category: Allergy & Immunology Authors: Tags: Clin Exp Immunol Source Type: research