The effects of the citrullinating enzyme, peptidylarginine deiminase, on the activation of T cells

Abstract

Rheumatoid arthritis (RA) and periodontitis (PID) are two chronic inflammatory diseases associated with the modification of self-proteins by citrullinating peptidyl arginine deiminase (PAD) enzymes, leading to a loss of tolerance by the immune system. The main goal of this study was to explore the action of PAD enzymemediated citrullination on T cell membrane proteins and gene expression in relation to the T cell phenotype in PID. Effects on cells of the adaptive immune system have been less well studied in PID and the data obtained here shows that citrullination of peripheral blood mononuclear cells (PBMC) by PAD enzymes impairs T cell activation. Microarray studies showed that PAD enzyme treatment led to the dysregulation of genes involved in glucose and amino acid metabolism in PBMC. Real time quantitative polymerase chain reaction (RT-QPCR) in CD4 and CD8 T cells from PID patients showed a trend towards down-regulation of hexokinase 3 and up-regulation of argininosuccinate synthase1. Also, proteomic and genomic studies in PBMC implicated the involvement of the complement system in the impairment of the T cell response by PAD enzymes. Taken together, the results obtained here support a potential link between T cell surface citrullination and metabolic asynchrony in T cells and may offer an explanation for the lack of immune suppression in PID.