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TNFR2 promotes Treg-mediated recovery from neuropathic pain across sexes
Journal article   Open access

TNFR2 promotes Treg-mediated recovery from neuropathic pain across sexes

Roman Fischer, Maksim Sendetski, Tania Del Rivero, George F Martinez, Valerie Bracchi-Ricard, Kathryn A Swanson, Elizabeth K Pruzinsky, Niky Delguercio, Michael J Rosalino, Tanja Padutsch, …
Proceedings of the National Academy of Sciences - PNAS, v 116(34), pp 17045-17050
20 Aug 2019
DOI: https://doi.org/10.1073/pnas.1902091116
PMID: 31391309
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1073/pnas.1902091116View
Published, Version of Record (VoR)CC BY-NC-ND V4.0,  Open

Abstract

Animals Chronic Pain - genetics Chronic Pain - immunology Chronic Pain - pathology Chronic Pain - therapy Female Inflammation - genetics Inflammation - immunology Inflammation - pathology Lymphocyte Depletion Male Mice Mice, Knockout Neuralgia - genetics Neuralgia - immunology Neuralgia - pathology Neuralgia - therapy Receptors, Tumor Necrosis Factor, Type II - genetics Receptors, Tumor Necrosis Factor, Type II - immunology Signal Transduction - genetics Signal Transduction - immunology T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - pathology
Tumor necrosis factor receptor 2 (TNFR2) is a transmembrane receptor that is linked to immune modulation and tissue regeneration. Here, we show that TNFR2 essentially promotes long-term pain resolution independently of sex. Genetic deletion of TNFR2 resulted in impaired neuronal regeneration and chronic nonresolving pain after chronic constriction injury (CCI). Further, pharmacological activation of TNFR2 using the TNFR2 agonist EHD2-sc-mTNF in mice with chronic neuropathic pain promoted long-lasting pain recovery. TNFR2 agonist treatment reduced neuronal injury, alleviated peripheral and central inflammation, and promoted repolarization of central nervous system (CNS)-infiltrating myeloid cells into an antiinflammatory/reparative phenotype. Depletion of regulatory T cells (Tregs) delayed spontaneous pain recovery and abolished the therapeutic effect of EHD2-sc-mTNF This study therefore reveals a function of TNFR2 in neuropathic pain recovery and demonstrates that both TNFR2 signaling and Tregs are essential for pain recovery after CCI. Therefore, therapeutic strategies based on the concept of enhancing TNFR2 signaling could be developed into a nonopioid therapy for the treatment of chronic neuropathic pain.

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UN Sustainable Development Goals (SDGs)

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#3 Good Health and Well-Being

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Domestic collaboration
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Web of Science research areas
Neurosciences
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