Modulation of regulatory T cells in health and disease: role of toll-like receptors.

Naturally arising regulatory T cells (Tregs) originate from the thymus and are characterised by the expression of Foxp3 as a key control gene for their development and function. Their pivotal role is maintaining immunological self tolerance. Recently, Tregs have been shown to express Toll-like receptors (TLRs), which are essential components of the innate immune system for the detection of microbial infections and the activation of dendritic cells (DC) maturation programs to induce adaptive immune responses. TLRs are type 1 transmembrane receptors characterised by a highly variable extracellular region containing a leucine rich repeat domain (LRR) involved in ligand binding and an intracellular tail containing a highly conserved region, the TIR homology domain, which mediates interaction between TLRs and downstream signalling molecules. Recent data suggest that the activation of TLRs on Tregs can increase or decrease their suppressive activity, thus providing an important link between innate and adaptive immune responses. Treg modulation by TLRs might influence such processes as the response to infections, immune surveillance to cancer, transplant rejection, and the induction of autoimmunity. Understanding the link between Tregs and TLR could be beneficial to the discovery of new therapeutic targets and strategies.