OBJECTIVE:To investigate the therapeutic effects of adeno-associated virus serotype 8 (AAV8)-mediated delivery of the extracellular domain of IL-17RA (IL-17RA(ECD)) on imiquimod (IMQ)-induced psoriasiform dermatitis in mice.
METHODS:A recombinant AAV core plasmid encoding murine IL-17RA-ECD (pAAV-mIL17RA(ECD)) was generated by gene synthesis and validated for secretory expression in HEK293T cells. The recombinant AAV8 vector carrying mIL-17RA(ECD) was produced by co-transfection of pAAV-mIL17RA(ECD), helper plasmid, and AAV8 capsid plasmid. In vivo, mice were divided into four groups (Vaseline, IMQ, Luciferase+IMQ, and IL-17RA+IMQ; n = 5 per group). On day 1, mice in the treatment group received subcutaneous injections of AAV8 vector encoding luciferase or mIL-17RA(ECD). Disease progression was monitored through body weight, photography, and PASI scoring. Histopathological changes were assessed by H&E staining, and potential viral toxicity was examined in heart, liver, lung, and kidney tissues. Expression of inflammatory cytokines (TNF-α, IL-6, IL-1β，Defb4) at both mRNA and protein levels was measured by qPCR and ELISA.
RESULTS:The recombinant plasmid pAAV-mIL17RA(ECD) was successfully constructed and demonstrated efficient secretory expression. AAV8-mediated mIL-17RA(ECD) expression significantly alleviated IMQ-induced psoriasiform dermatitis (P < 0.05) and markedly suppressed the upregulation of inflammatory cytokines in skin and serum at both transcriptional and protein levels (P < 0.05).
CONCLUSION:AAV8-mediated IL-17RA(ECD) gene delivery effectively blocks cutaneous inflammation and attenuates inflammatory cytokines overexpression in an IMQ-induced mouse model of psoriasis, highlighting its therapeutic potential for chronic inflammatory skin diseases.
