Role of T Cells in the Pathogenesis of Rheumatoid Arthritis: Focus on Immunometabolism Dysfunctions.

Evidence demonstrated that metabolic-associated T cell abnormalities could be detected in the early stage of RA development. In this context, molecular evaluations have revealed changes in metabolic pathways, leading to the aggressive phenotype of RA T cells. A growing list of genes is downregulated or upregulated in RA T cells, and most of these genes with abnormal expression fall into the category of metabolic pathways. It has been shown that RA T cells shunt glucose towards the pentose phosphate pathway (PPP), which is associated with a high level of nicotinamide adenine dinucleotide phosphate (NADPH) and intermediate molecules. An increased level of NADPH inhibits ATM activation and thereby increases the proliferation capabilities of the RA T cells. Defects in the DNA repair nuclease MRE11A cause failures in repairing mitochondrial DNA, resulting in inhibiting the fatty acid oxidation pathway and further elevated cytoplasmic lipid droplets. Accumulated lipid droplets employ to generate lipid membranes for the cell building program and are also used to form the front-end membrane ruffles that are accomplices with invasive phenotypes of RA T cells. Metabolic pathway involvement in RA pathogenesis expands the pathogenic concept of the disease beyond the common view of autoimmunity triggered by autoantigen recognition. Increased knowledge about metabolic pathways' implications in RA pathogenesis paves the way to understand better the environment/gene interactions and host/microbiota interactions and introduce potential therapeutic approaches. This review summarized emerging data about the roles of T cells in RA pathogenesis with a focus on immunometabolism dysfunctions and how these metabolic alterations can affect the disease process.