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Integrated systems toxicology identifies TCDD-responsive targets linked to immune dysregulation and treatment

Xuan Zhang1, Yankun Zhang1, Yanling He1

  • 1Department of Dermatology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Frontiers in Medicine
|June 15, 2026
PubMed
Abstract

Insights

Environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) may influence psoriasis by affecting immune pathways and core genes like LCK and MMP9. Further research is needed to confirm the link between TCDD exposure and psoriasis development and treatment response.

Area of Science:

  • Dermatology
  • Toxicology
  • Immunology

Background:

  • Psoriasis is a chronic, immune-mediated inflammatory skin disease linked to the IL-23/IL-17 axis.
  • The impact of environmental pollutants like 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on psoriasis pathogenesis is not well understood.
  • Investigating TCDD's molecular mechanisms in psoriasis is crucial for understanding disease etiology.

Purpose of the Study:

  • To systematically investigate the potential toxicity and molecular mechanisms of TCDD in psoriasis.
  • To identify TCDD-associated genes and pathways involved in psoriasis immune dysregulation.
  • To explore the relationship between TCDD exposure, psoriasis development, and treatment response.

Main Methods:

  • An integrative strategy combining network toxicology, machine learning, bioinformatics, and molecular simulation.
  • Identification of overlapping genes between TCDD targets and psoriasis-associated genes.
  • In vitro validation using keratinocyte quantitative reverse transcription PCR (qRT-PCR).

Main Results:

  • Eighty-seven overlapping genes were identified, enriched in IL-17, chemokine, MAPK/ERK, and GPCR pathways.
  • Five core genes (LCK, MMP9, CXCR2, PTAFR, CCNB1) were identified, upregulated in psoriatic lesions.
  • TCDD exposure altered keratinocyte gene expression, and higher baseline MMP9 correlated with poorer treatment response.

Conclusions:

  • Integrative analyses suggest TCDD-associated genes and pathways contribute to psoriasis immune dysregulation.
  • In silico and in vitro findings support TCDD's potential interaction with CXCR2 and dysregulation of core genes in epidermal cells.
  • Further validation in cohort studies is necessary to establish a definitive link between TCDD exposure and psoriasis.
Keywords:
2378-tetrachlorodibenzo-p-dioxinimmune dysregulationnetwork toxicologypsoriasistreatment response

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