TNFα in the regulation of Treg and Th17 cells in rheumatoid arthritis and other autoimmune inflammatory diseases

T cells both produce and respond to TNFα and depending on whether the cytokine is membrane-bound or soluble and the level of expression of its two receptors, the biological outcome can be distinct. In addition, polymorphisms in genes encoding TNFα and T cell signalling proteins can significantly impact the outcome of TNFα receptor engagement. Early studies revealed that effector T cells in patients with rheumatoid arthritis (RA) are hyporesponsive due to chronic exposure to TNFα. However, recent evidence indicates that the relationship between TNFα and T cell responses is complex and, at times, can be paradoxical. In addition, there is controversy as to the specific effects of TNFα on different T cell subsets. This review will summarise knowledge on how TNFα modulates T cell responses and the effect of engaging either of its two receptors. Furthermore, we discuss how such interactions can dictate the outcome of treatment with TNFα inhibitors.