The expression of cytokines and chemokines potentially distinguishes mild and severe psoriatic non-lesional and resolved skin from healthy skin and indicates different stages of inflammation

Bozó, Renáta and Flink, Lili Borbála and Ambrus, Barbara and Ghaffarinia, Ameneh and Koncz, Balázs and Kui, Róbert and Gyulai, Rolland Péter and Kemény, Lajos and Csörgő Sándorné Bata, Zsuzsanna (2024) The expression of cytokines and chemokines potentially distinguishes mild and severe psoriatic non-lesional and resolved skin from healthy skin and indicates different stages of inflammation. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 25 (20). ISSN 1661-6596

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Abstract

In the psoriatic non-lesional (PS-NL) skin, the tissue environment potentially influences the development and recurrence of lesions. Therefore, we aimed to investigate mechanisms involved in regulating tissue organization in PS-NL skin. Cytokine, chemokine, protease, and protease inhibitor levels were compared between PS-NL skin of patients with mild and severe symptoms and healthy skin. By comparing mild and severe PS-NL vs. healthy skin, differentially expressed cytokines and chemokines suggested alterations in hemostasis-related processes, while protease inhibitors showed no psoriasis severity-related changes. Comparing severe and mild PS-NL skin revealed disease severity-related changes in the expression of proteases, cytokines, and chemokines primarily involving methyl-CpG binding protein 2 (MECP2) and extracellular matrix organization-related mechanisms. Cytokine and chemokine expression in clinically resolved versus healthy skin showed slight interleukin activity, differing from patterns in mild and severe PS-NL skin. Immunofluorescence analysis revealed the severity-dependent nuclear expression pattern of MECP2 and decreased expression of 5-methylcytosine and 5-hydroxymethylcytosine in the PS-NL vs. healthy skin, and in resolved vs. healthy skin. Our results suggest distinct cytokine-chemokine signaling between the resolved and PS-NL skin of untreated patients with varying severities. These results highlight an altered inflammatory response, epigenetic regulation, and tissue organization in different types of PS-NL skin with possibly distinct, severity-dependent para-inflammatory states.

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