Regulatory T cells attenuate neuropathic pain following peripheral nerve injury and experimental autoimmune neuritis.
Neuroimmune crosstalk in neuropathic pain is a key contributor to pain hypersensitivity following nervous system injury. CD4+CD25+Foxp3+ regulatory T cells (Tregs) are endogenous immune suppressors, reducing T-cell proliferation and proinflammatory cytokine production. Currently, the role of Tregs in neuropathic pain is unknown. In this study, we tested the effects of expanding Tregs on pain hypersensitivity and neuroinflammation in 2 models of neuropathy; sciatic nerve chronic constriction injury and experimental autoimmune neuritis in rats. Following chronic constriction injury, treatment with CD28 superagonist (CD28SupA), a Treg population expander, significantly increased Tregs in the lymphoid tissues, injured sciatic nerve, and lumbar spinal cord of rats. CD28SupA treatment led to a significant reduction in mechanical pain hypersensitivity, alongside a decrease in the numbers of infiltrating T cells, macrophages, and antigen-presenting cells in the sciatic nerve and dorsal root ganglia. In experimental autoimmune neuritis-affected rats, CD28SupA treatment resulted in a significant improvement in disease severity and in mechanical pain hypersensitivity. This was associated with a reduction in the numbers of T cells, macrophages, and antigen-presenting cells in the sciatic nerve and dorsal root ganglia, and reduced activation of microglia and infiltration of T cells in the spinal cord. Furthermore, depletion of Tregs by a CD25 antibody in mice with a partial sciatic nerve ligation resulted in prolonged mechanical pain hypersensitivity. These findings suggest that Tregs play a role in endogenous recovery from neuropathy-induced pain. Thus, this T-cell subset may be specifically targeted to alleviate chronic neuropathic pain.
School of Medical Sciences, University of New South Wales, Sydney NSW 2052, Australia.
Paul J
PJ
Austin
Cristina F
CF
Kim
Chamini J
CJ
Perera
Gila
G
Moalem-Taylor
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D006930:Hyperalgesia / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000276:immunology*; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000293:injuries; D020426:Sciatic Neuropathy / Q000209:etiology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*