5-HT7R enhances neuroimmune resilience and alleviates meningitis by promoting CCR5 ubiquitination.
J Adv Res
; 2024 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-38432392
ABSTRACT
INTRODUCTION:
Excessive immune activation induces tissue damage during infection. Compared to external strategies to reconstruct immune homeostasis, host balancing ways remain largely unclear.OBJECTIVES:
Here we found a neuroimmune way that prevents infection-induced tissue damage.METHODS:
By FACS and histopathology analysis of brain Streptococcus pneumonia meningitis infection model and behavioral testing. Western blot, co-immunoprecipitation, and ubiquitination analyze the Fluoxetine initiate 5-HT7R-STUB1-CCR5 K48-linked ubiquitination degradation.RESULTS:
Fluoxetine, a selective serotonin reuptake inhibitor, or the agonist of serotonin receptor 5-HT7R, protects mice from meningitis by inhibiting CCR5-mediated excessive immune response and tissue damage. Mechanistically, the Fluoxetine-5-HT7R axis induces proteasome-dependent degradation of CCR5 via mTOR signaling, and then recruits STUB1, an E3 ubiquitin ligase, to initiate K48-linked polyubiquitination of CCR5 at K138 and K322, promotes its proteasomal degradation. STUB1 deficiency blocks 5-HT7R-mediated CCR5 degradation.CONCLUSION:
Our results reveal a neuroimmune pathway that balances anti-infection immunity via happiness neurotransmitter receptor and suggest the 5-HT7R-CCR5 axis as a potential target to promote neuroimmune resilience.
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Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article