Regulation of CD4+ T cell function by TNF blockade
Effector CD4+ T cells are important contributors to the chronic joint inflammation in rheumatoid arthritis (RA), through their production of pro-inflammatory cytokines. Importantly, effector CD4+ T cells can also produce the potent anti-inflammatory cytokine interleukin-10 (IL-10), thereby limiting excessive tissue damage. Detailed understanding of how IL-10 is regulated is therefore scientifically and clinically important.
Our lab previously demonstrated that tumour necrosis factor (TNF)-blocking drugs, which are widely used in the treatment of RA, promote IL-10 expression in human CD4+ T cells. We now aim to determine the molecular mechanisms via which TNF blockade regulates the expression of IL-10 in human pro-inflammatory CD4+ T cells and to determine what the functional consequences are. Using molecular, genetic, epigenetic, bioinformatics, flow cytometric, cellular and CyTOF analysis we study how TNF blockade influences regulation of IL-10 in human pro-inflammatory CD4+ T cells at the DNA, RNA and protein level. We also study the function and stability of TNF-blockade-induced IL-10 expressing CD4+ T cells. Through this work, we hope to reveal new molecular mechanisms of TNF blockade and possible biomarkers of response to anti-TNF therapy.
Versus arthritis research project determining the molecular mechanisms