Regulatory T cells counteract neuropathic pain through inhibition of the Th1 response at the site of peripheral nerve injury
Marcela Davoli-Ferreira, Kalil Alves de Lima, Miriam M. Fonseca, Rafaela Mano Guimarães, Francisco Isaac Fernandes Gomes, Maria CM Cavallini, Andreza Urba de Quadros, Ricardo Kusuda, Fernando Q. Cunha, José C. Alves‐Filho, Thiago M. Cunha
Abstract
The inflammatory/immune response at the site of peripheral nerve injury participates in the pathophysiology of neuropathic pain. Nevertheless, little is known about the local regulatory mechanisms underlying peripheral nerve injury that counteracts the development of pain. Here, we investigated the contribution of regulatory T (Treg) cells to the development of neuropathic pain by using a partial sciatic nerve ligation model in mice. We showed that Treg cells infiltrate and proliferate in the site of peripheral nerve injury. Local Treg cells suppressed the development of neuropathic pain mainly through the inhibition of the CD4 Th1 response. Treg cells also indirectly reduced neuronal damage and neuroinflammation at the level of the sensory ganglia. Finally, we identified IL-10 signaling as an intrinsic mechanism by which Treg cells counteract neuropathic pain development. These results revealed Treg cells as important inhibitory modulators of the immune response at the site of peripheral nerve injury that restrains the development of neuropathic pain. In conclusion, the boosting of Treg cell function/activity might be explored as a possible interventional approach to reduce neuropathic pain development after peripheral nerve damage.