Integrated Multi-Omics Profiling Reveals That Highly Pyroptotic MDMs Contribute to Psoriasis Progression Through...

Area of Science:

• Dermatology
• Immunology
• Cell Biology

Background:

• Psoriasis is an inflammatory skin disease.
• Pyroptosis, a pro-inflammatory cell death, is implicated but its cell-specific roles and immune interactions in psoriasis are unclear.

Purpose of the Study:

• Investigate cell-type-specific pyroptosis patterns in psoriasis.
• Elucidate the immunoregulatory mechanisms driving psoriasis pathogenesis.

Main Methods:

• Integrated 21 transcriptomic datasets and single-cell RNA sequencing data.
• Quantified pyroptotic activity using GSVA and AUCell algorithms.
• Analyzed immune cell infiltration (CIBERSORT) and cell-cell communication (CellChat).

Main Results:

• Psoriasis patients showed elevated pyroptosis, correlating with treatment response.
• Monocyte-derived macrophages (MDMs) in psoriatic lesions exhibited heightened pyroptosis.
• MDMs overexpressed pyroptosis molecules, pro-inflammatory cytokines, and CXCL16, potentially activating Th17 cells.

Conclusions:

• MDMs in psoriasis lesions display a hyperactive pyroptotic state.
• This contributes to disease progression via CXCL16-mediated immune microenvironment remodeling.
• Pyroptosis represents a potential therapeutic target for psoriasis.