Regulatory T cells restrain skin inflammation by modulating nociception

ABSTRACT: The skin, as a principal barrier tissue, integrates diverse signals discerned by sensory neurons and by immune cells to elicit adaptive responses to a wide range of stresses. While nociceptors, sensory neurons that initiate the sensation of pain, can mobilize and amplify the function of innate and adaptive immune effector cells, regulatory T (Treg) cells, a T cell subset expressing the transcription factor Foxp3, suppress systemic and local inflammatory responses. Considering the connectivity between nervous and immune systems for sensing and responding to damaging insults, we questioned whether Treg cells can modulate proinflammatory neuronal activity by acting directly on peripheral neurons. We found that Treg cells localized near axons innervating the skin and that short-term inactivation or ablation of Treg cells increased neuronal activation to noxious stimuli in a manner separable from their immunosuppressive function. Furthermore, a population of skin Treg cells was highly enriched for expression of Penk, the gene encoding the neuropeptide precursor for endogenous opioids enkephalins, which inhibit pain perception by inducing analgesia. Acute depletion of Penk expressing Treg cells, or inducible ablation of Penk in Treg cells increased neuronal activation in response to noxious stimuli and associated inflammation. Our study suggests that a population of Treg cells residing at barrier tissues exhibit a direct neuromodulatory activity opposing exacerbated activation of sensory neurons, at least in part through the production of an endogenous opioids, and by acting as an immune component of the neuro-immune axis, dampen responses to noxious pain stimuli and local inflammation.

ORGANISM(S): Mus musculus

PROVIDER: GSE218063 | GEO | 2023/11/14

REPOSITORIES: GEO