Objective:

To investigate the potential toxicity and molecular mechanisms of TCDD in psoriasis using an integrative approach, focusing on specific pathways and gene interactions.

Key Findings:

• Eighty-seven overlapping genes were identified between TCDD-related targets and psoriasis-associated genes, enriched in IL-17-, chemokine-, MAPK/ERK-, and GPCR-related signaling pathways.
• Core target genes LCK, MMP9, CXCR2, PTAFR, and CCNB1 were significantly upregulated in psoriatic lesions and associated with local immune infiltration patterns.
• Higher baseline MMP9 was associated with poorer clinical improvement in biologic-therapy cohorts.

Interpretation:

The study identifies TCDD-associated genes and pathways involved in psoriasis immune dysregulation, with structural modeling suggesting interactions between TCDD and CXCR2.

Limitations:

• The study relied mainly on in silico analyses without individual-level exposure data.
• Further validation in well-designed cohort studies is needed to confirm these findings.

Conclusion:

The findings provide insights into TCDD's role in psoriasis, highlighting the associations identified without making unsupported claims about future research needs.