| First Author | Sugisawa E | Year | 2022 |
| Journal | Cell Rep | Volume | 38 |
| Issue | 10 | Pages | 110462 |
| PubMed ID | 35263589 | Mgi Jnum | J:324853 |
| Mgi Id | MGI:7281952 | Doi | 10.1016/j.celrep.2022.110462 |
| Citation | Sugisawa E, et al. (2022) Nociceptor-derived Reg3gamma prevents endotoxic death by targeting kynurenine pathway in microglia. Cell Rep 38(10):110462 |
| abstractText | Nociceptors can fine-tune local or systemic immunity, but the mechanisms of nociceptive modulation in endotoxic death remain largely unknown. Here, we identified C-type lectin Reg3gamma as a nociceptor-enriched hormone that protects the host from endotoxic death. During endotoxemia, nociceptor-derived Reg3gamma penetrates the brain and suppresses the expression of microglial indoleamine dioxygenase 1, a critical enzyme of the kynurenine pathway, via the Extl3-Bcl10 axis. Endotoxin-administered nociceptor-null mice and nociceptor-specific Reg3gamma-deficient mice exhibit a high mortality rate accompanied by decreased brain HK1 phosphorylation and ATP production despite normal peripheral inflammation. Such metabolic arrest is only observed in the brain, and aberrant production of brain quinolinic acid, a neurotoxic metabolite of the kynurenine pathway, causes HK1 suppression. Strikingly, the central administration of Reg3gamma protects mice from endotoxic death by enhancing brain ATP production. By identifying nociceptor-derived Reg3gamma as a microglia-targeted hormone, this study provides insights into the understanding of tolerance to endotoxic death. |
