CARD14 expression in dermal endothelial cells in psoriasis

Area of Science:

• Dermatology
• Immunology
• Genetics

Background:

• Mutations in the CARD14 gene are linked to psoriasis (PSORS2).
• CARD14 protein regulates NF-κB signaling, and mutations enhance this pathway.
• CARD14 is found in epidermal keratinocytes and unidentified dermal cells.

Purpose of the Study:

• Identify dermal cell types expressing CARD14.
• Investigate the functional consequences of CARD14 overactivation in these cells.
• Explore the role of CARD14 in psoriasis pathogenesis.

Main Methods:

• Two-color immunofluorescence to detect CARD14 co-localization with dermal cell markers.
• Analysis of NF-κB phosphorylation in psoriatic skin.
• Transfection of dermal ECs with CARD14 mutations to assess chemokine expression.

Main Results:

• Dermal CARD14 highly co-localized with CD31(+) endothelial cells (ECs), not immune cells.
• CARD14 was also expressed in non-dermal ECs, suggesting a systemic role.
• Phosphorylated NF-κB was detected in psoriatic CARD14(+) CD31(+) ECs.
• Psoriatic CARD14 mutations in dermal ECs increased expression of CXCL10, IL-8, and CCL2.

Conclusions:

• CARD14 is expressed in dermal ECs and its activity is increased in psoriasis.
• CARD14(+) ECs may contribute to psoriasis by releasing chemokines that recruit immune cells.
• CARD14 in ECs could play a role in systemic inflammation and cardiovascular comorbidities associated with psoriasis.