Itch control by Toll-like receptors

Toll-like receptors (TLRs) are cellular sensors designed to recognize molecular danger signals associated with exogenous or endogenous threats. Their activation leads to initiation of the host's immune responses in order to remove or contain the danger. However, one of the most effective methods of defense against invading pathogens and parasites is itch. The perception of itch elicits the rapid defensive action to scratch, which can remove the offending pathogen or parasite before infection can occur. Recent findings show that TLRs such as TLR3, TLR4, and TLR7 are expressed in a subset of pruriceptive/nociceptive neurons in the dorsal root and trigeminal ganglion providing a direct link between TLR activation and itch. Activation of neuronal TLRs can initiate itch sensation by coupling with ion channels. Furthermore, TLRs are expressed in skin cells and glial cells in the spinal cord to regulate inflammation and neuroinflammation in chronic itch. Thus, identification of the role of TLRs in neurons, skin cells, and glial cells may provide new targets for the treatment of chronic itch, a common clinical problem associated with skin diseases, systemic diseases, and metabolic disorders, for which current treatments are far from sufficient.