Characterization of chromatin accessibility in psoriasis

Area of Science:

• Immunology
• Epigenetics
• Dermatology

Background:

• Psoriasis pathogenesis involves T cell gene alterations at the transcriptional level, influenced by chromatin accessibility.
• The precise epigenetic landscape of T cells in psoriasis remains incompletely understood.

Purpose of the Study:

• To systematically profile chromatin accessibility and transcriptional dynamics in various T cell subtypes during psoriasis.
• To identify key regulatory factors and networks involved in the epigenetic mechanisms of psoriasis.

Main Methods:

• Chromatin accessibility profiling (ATAC-seq) was performed on distinct T helper (Th) cell subsets (Th1, Th2, Th1-17, Th17, regulatory T cells [Tregs]) and memory Th/Treg cells.
• Transcriptional dynamics were analyzed alongside chromatin accessibility data.
• Differential gene expression and regulatory network analysis were conducted.

Main Results:

• Chromatin remodeling was identified as a significant contributor to psoriasis pathogenesis, with consistent remodeling tendencies across Th cell subtypes.
• Significant alterations in chromatin accessibility were observed in memory Th and Treg cells, with thousands of regions showing increased or decreased accessibility.
• Key regulatory transcription factors, including NFKB1 and RELA, were identified as central to the psoriasis transcriptional regulatory network, controlling genes like CCL3, CXCL2, and IL1RN.

Conclusions:

• Epigenetic alterations, specifically chromatin remodeling in T cells, play a crucial role in the pathogenesis of psoriasis.
• The study provides a foundational framework of T cell regulomes in psoriasis and identifies candidate transcription factors for therapeutic targeting.