TRPV1 channel mediates NLRP3 inflammasome-dependent neuroinflammation in microglia

Cell Death Dis. 2021 Dec 14;12(12):1159. doi: 10.1038/s41419-021-04450-9.


Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease in the central nervous system (CNS). The NLRP3 inflammasome is considered an important regulator of immunity and inflammation, both of which play a critical role in MS. However, the underlying mechanism of NLRP3 inflammasome activation is not fully understood. Here we identified that the TRPV1 (transient receptor potential vanilloid type 1) channel in microglia, as a Ca2+ influx-regulating channel, played an important role in NLRP3 inflammasome activation. Deletion or pharmacological blockade of TRPV1 inhibited NLRP3 inflammasome activation in microglia in vitro. Further research revealed that TRPV1 channel regulated ATP-induced NLRP3 inflammasome activation through mediating Ca2+ influx and phosphorylation of phosphatase PP2A in microglia. In addition, TRPV1 deletion could alleviate mice experimental autoimmune encephalomyelitis (EAE) and reduce neuroinflammation by inhibiting NLRP3 inflammasome activation. These data suggested that the TRPV1 channel in microglia can regulate NLRP3 inflammasome activation and consequently mediate neuroinflammation. Meanwhile, our study indicated that TRPV1-Ca2+-PP2A pathway may be a novel regulator of NLRP3 inflammasome activation, pointing to TRPV1 as a potential target for CNS inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Encephalomyelitis, Autoimmune, Experimental* / genetics
  • Encephalomyelitis, Autoimmune, Experimental* / metabolism
  • Inflammasomes* / metabolism
  • Mice
  • Microglia* / metabolism
  • Multiple Sclerosis / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Neuroinflammatory Diseases
  • TRPV Cation Channels* / genetics
  • TRPV Cation Channels* / metabolism


  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • TRPV Cation Channels
  • TRPV1 protein, mouse