AI Article Synopsis

  • - Psoriasis is a chronic skin condition linked to immune system dysfunction and oxidative stress, with the neonatal Fc receptor (FcRn) playing a potential role in its severity according to clinical analyses.
  • - In a mouse model of psoriasis, researchers found lower levels of FcRn in affected skin, and the ferroptosis pathway was activated, suggesting that FcRn may influence this process through the STAT3/SLC7A11 signaling pathway.
  • - Experiments indicated that depleting FcRn increased psoriatic lesions and ferroptosis, while inhibiting this process or activating FcRn improved symptoms, pointing to possible new treatments for psoriasis.

Article Abstract

Psoriasis, a chronic inflammatory skin disease, is characterized by complex immune dysregulation and oxidative stress responses. The neonatal Fc receptor (FcRn) plays a crucial role in the development of autoimmune diseases. Analysis of clinical psoriasis samples demonstrated a negative correlation between FcRn expression in skin lesions and disease severity. However, the role of FcRn in this process remains unclear. This study aimed to investigate the involvement of FcRn in the pathogenesis and progression of psoriasis. In an imiquimod (IMQ)-induced psoriasis-like mouse model, FcRn expression was significantly decreased in the lesional skin, and transcriptome sequencing of the skin revealed activation of the ferroptosis pathway in psoriasis. This led to the hypothesis that FcRn could potentially regulate ferroptosis via the signal transducer and activating transcription factor 3 (STAT3)/solute carrier family 7 member 11 (SLC7A11) axis. Further experiments showed exacerbated psoriasis-like lesional skin and ferroptosis in FcRn-knockout mice, whereas intervention with the ferroptosis inhibitor Fer-1 or STAT3 inhibitor Stattic alleviated these symptoms. Critical binding sites for the transcription factor STAT3 were identified in the SLC7A11 promoter region at positions -1185 and -564 using the luciferase reporter assays and chromatin immunoprecipitation. The administration of 1,4-naphthoquinone (NQ), an FcRn agonist, effectively alleviated psoriasis-like skin lesions by inhibiting ferroptosis. This study highlights the molecular mechanisms of action of FcRn in psoriasis and provides an experimental basis for the development of novel therapeutic strategies targeting FcRn.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.freeradbiomed.2024.09.010DOI Listing

Publication Analysis

Top Keywords

lesional skin
12
fcrn
10
novel therapeutic
8
fcrn expression
8
skin lesions
8
transcription factor
8
skin
7
psoriasis
6
ferroptosis
6
therapeutic approach
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!