Furthermore, it upregulates the production of GM-CSF, prostaglandins, and collagenases as well as ICAM-1 by synovial fibroblasts (199–202) The importance of TNF-α for regulatory T cells in RA is highlighted by studies showing an increased Treg suppressive activity as well as an increase in Treg/Teff balance under treatment with the TNF-α antagonist Infliximab as well as a reduction in Treg numbers in TTG mice overexpressing hTNF-α. This evidence concerns the gene TNF and rheumatoid arthritis.