Effects of Adalimumab on Mitochondria of Psoriatic Mesenchymal Stem Cells

Abstract

Psoriasis is a systemic immune-mediated disorder involving multiple signalling pathways. Recent attempts to treat psoriasis involve monoclonal antibodies that block different inflammatory pathways. The monoclonal antibody Adalimumab (ADM) is one of the biologics that block the inflammatory cascade of TNF-alpha. We previously demonstrated the involvement of mesenchymal stem cells (MSCs) in psoriasis pathogenesis and showed their responsiveness to ADM, highlighting their dual role as contributors and therapeutic targets. Mitochondrial dysfunction is increasingly recognised in psoriasis, contributing to oxidative stress, altered metabolism, and immune dysregulation. These mitochondrial changes drive chronic inflammation, keratinocyte hyperproliferation, and immune activation—hallmarks of psoriasis—making mitochondria a key focus for therapeutic strategies. In this study, we further investigated ADM's impact on mitochondrial morphology and function in MSCs. MSCs were isolated from the skin of psoriatic patients (PSO-MSCs) and healthy controls (C-MSCs), then exposed to H₂O₂ or LPS to mimic the oxidative and inflammatory environment of psoriasis. PSO-MSCs were also treated with ADM for 72 h before mitochondrial analysis. Compared to C-MSCs, PSO-MSCs showed marked mitochondrial abnormalities. ADM treatment partially reversed these alterations, restoring mitochondrial parameters toward control levels under basal conditions. However, ADM failed to prevent mitochondrial dysfunction when additional stress (H₂O₂ or LPS) was introduced. In conclusion, ADM exerts a protective effect on mitochondrial health in MSCs from psoriatic patients, suggesting mitochondria are among its therapeutic targets. Nonetheless, ADM alone cannot counteract further environmental or inflammatory stressors, which may explain symptom relapse observed in clinical settings.