Chronic inflammatory arthritis, a hallmark of a variety of inflammatory rheumatic diseases, such as rheumatoid arthritis (RA) and spondyloarthritis (SpA), is a significant health problem in our society with a major socio-economic impact. Mechanisms contributing to these pathogenic conditions are largely TNF dependent. Invariant natural killer T cells (iNKT) and CD4+CD25+FOXP3+ regulatory T cells (Tregs) are important thymus-derived immunomodulatory cells. iNKT cells are well known for their capacity to secrete copious amounts of T helper (Th)1 and Th2 cytokines upon recognition of glycolipids presented by CD1d molecules on antigen presenting cells, thereby influencing various immune responses. Tregs are able to suppress the activation and effector function of a variety of immune cells by which they can modulate, predominantly suppress, immune responses. Whether there is a direct crosstalk between these cell types under chronic inflammatory conditions is yet unclear. In this project, we therefore aim to evaluate the functional interaction between these immunomodulatory cells in patients with inflammatory rheumatic disorders. Furthermore, the cooperation of iNKT cells and Tregs under inflammatory conditions will be evaluated in an animal model of TNF mediated arthritis. A better understanding of immunoregulatory networks may significantly contribute to our ability to optimize treatment modalities for rheumatic diseases.