GT1b functions as a novel endogenous agonist of toll-like receptor 2 inducing neuropathic pain

Hyoungsub Lim, Jaesung Lee, Byunghyun You, Jae Hoon Oh, Hyuck Jun Mok, Yoo Sung Kim, Bo Eun Yoon, Byung Gon Kim, Seung Keun Back, Jong Sang Park, Kwang Pyo Kim, Ronald L. Schnaar, Sung Joong Lee

Research output: Contribution to journalArticlepeer-review

Abstract

Spinal cord microglia contribute to nerve injury-induced neuropathic pain. We have previously demonstrated that toll-like receptor 2 (TLR2) signaling is critical for nerve injury-induced activation of spinal cord microglia, but the responsible endogenous TLR2 agonist has not been identified. Here, we show that nerve injury-induced upregulation of sialyltransferase St3gal2 in sensory neurons leads to an increase in expression of the sialylated glycosphingolipid, GT1b. GT1b ganglioside is axonally transported to the spinal cord dorsal horn and contributes to characteristics of neuropathic pain such as mechanical and thermal hypersensitivity. Spinal cord GT1b functions as an TLR2 agonist and induces proinflammatory microglia activation and central sensitization. Pharmacological inhibition of GT1b synthesis attenuates nerve injury-induced spinal cord microglia activation and pain hypersensitivity. Thus, the St3gal2-GT1b-TLR2 axis may offer a novel therapeutic target for the treatment of neuropathic pain.

Original languageEnglish (US)
Article numbere102214
JournalEMBO Journal
Volume39
Issue number6
DOIs
StatePublished - Mar 16 2020

Keywords

  • St3gal2
  • ganglioside
  • microglia
  • neuropathic pain
  • toll-like receptor 2

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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