Regulatory T cells promote sensory neuron growth and protect against neurotoxicity.

Regulatory T cells (Tregs) maintain immune homeostasis and suppress inflammation, and emerging evidence indicates they also modulate neuronal function and regeneration. Dorsal root ganglion (DRG) sensory neurons transmit pain signals and are damaged by chemotherapeutic agents such as paclitaxel (PTX), leading to neuropathic pain. Although Tregs show therapeutic promise in neuropathic pain, the mechanisms of Treg-neuron interactions remain poorly defined. Using in vitro co-culture, we examined interactions between primary DRG neurons and Tregs and their effect on PTX-induced neurotoxicity. Live-cell imaging showed that activated Tregs enhanced neurite length and branching and preferentially localised to neuron/neurite-rich regions. Additionally, activated Tregs rescued PTX-induced inhibition of neurite outgrowth. Pharmacological blockade identified Treg-derived amphiregulin (AREG) as essential for neurite outgrowth, while both AREG and neuropeptide Y were required for Treg-mediated protection against PTX-induced neurotoxicity. These findings identify Tregs as direct promoters of sensory neuron growth and protection from PTX-induced neurotoxicity through specific molecular mediators, supporting their potential therapeutic relevance in peripheral neuropathic pain.