PRELP negatively regulates IL-17A-mediated proliferation and the inflammatory response in psoriasis - PubMed
2 hours ago
- #PRELP
- #Psoriasis
- #IL-17A
- PRELP is upregulated in psoriasis skin lesions after IL-17A inhibitor treatment, but is downregulated in lesional vs. nonlesional skin at baseline.
- IL-17A suppresses PRELP expression in keratinocytes, which aligns with its reduced levels in both mouse models and human psoriatic lesions.
- PRELP inhibits keratinocyte proliferation, promotes apoptosis, and dampens NF-κB and MAPK pathway activation, reducing proinflammatory cytokine and chemokine production.
- By downregulating IL6, PRELP reduces local IL-17A production, breaking a feed-forward inflammatory loop in psoriasis.
- Intradermal AAV-K14-PRELP delivery alleviates psoriasis-like symptoms in mice, including erythema, scaling, epidermal hyperplasia, and Th17 cell infiltration.
- IL-17A represses PRELP transcription via STAT3 activation, where STAT3 binds directly to the PRELP promoter as a transcriptional repressor.
- PRELP acts as a negative regulator of IL-17A signaling in psoriasis, suggesting therapeutic potential for enhancing its expression in Th17-driven diseases.