Casting NETs on Psoriasis: The modulation of inflammatory feedback targeting IL-36/IL-36R axis.
Int Immunopharmacol
; 142(Pt B): 113190, 2024 Sep 21.
Article
em En
| MEDLINE
| ID: mdl-39306890
ABSTRACT
NETosis happens when neutrophils are activated and neutrophil extracellular traps (NETs) are formed synchronously, which is a hallmark of psoriasis. However, the specific trigger that drives NET formation and the distinct contents and interaction with interleukin-36 receptor (IL-36R) of NETs remain to be further elucidated. This work identified NET formation driven by toll-like receptor (TLR) 3 ligand (especially polyinosinic-polycytidylic acid (Poly(IC)) were enhanced by purinergic receptor P2X ligand-gated ion channel 7 receptor (P2X7R) ligands (especially adenosine 5'-triphosphate (ATP)). NET formation was accompanied by the secretion of inflammatory cytokines and characterized by IL-1ß decoration. NET formation blockade decreased expressions of inflammatory cytokines and chemokines, which consequently improved inflammatory responses. Additionally, imiquimod (IMQ)-induced psoriasiform symptoms including neutrophilic infiltration tended to be time-sensitive. Mouse primary keratinocytes and mice deficient in Il1rl2, which encodes IL-36R, mitigated inflammatory responses and NET formation, thereby delaying the pathophysiology of psoriasis. Together, the findings provided the therapeutic potential for IL-36 targeting NET inhibitors in psoriasis treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Int Immunopharmacol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de publicação:
Holanda