Abstract

T helper (Th) lymphocytes play a major role in the regulation of immune responses and are thought to initiate and drive chronic rheumatic inflammation. Memory Th lymphocytes persist in the inflamed tissue and are refractory to therapeutic intervention. In chronic inflammation Th lymphocytes have undergone molecular adaptations, such as the upregulation of Twist1 and the microRNA miR-148a, which are not found in circulating Th lymphocytes, and support the survival of the Th cells within the inflamed tissue. Within the inflamed tissue, the Th lymphocytes constantly recruit and activate inflammatory cells, such as monocytes/macrophages and granulocytes through the secretion of particular chemokines and interleukins. The monocytes/macrophages in turn can recruit more Th cells into the inflamed tissue. Disrupting this vicious circle by specifically targeting the memory Th cells resident in the inflamed tissue by interfering with their molecular adaptations could be an interesting therapeutic option.