Metabolic re‐programming of keratinocytes in response to contact allergens

• Published in: Contact dermatitis Vol. 90; no. 3; pp. 235 - 244
• Main Authors: Menzel, Mandy, Mraz, Veronika, Vaher, Helen, Geisler, Carsten, Menné Bonefeld, Charlotte
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2024; Wiley Subscription Services, Inc
• Subjects: Allergens; Allergens - adverse effects; allergic contact dermatitis; Atopic dermatitis; Biomarkers; Cell Line; Contact dermatitis; Dermatitis; Dermatitis, Allergic Contact; Dermatitis, Atopic; Flow cytometry; Gene expression; Glucose metabolism; Haptens; Humans; Immune response; Immune system; Keratinocytes; Keratinocytes - metabolism; Metabolic pathways; metabolic re‐programming; Metabolism; Oxidative metabolism; Oxidative phosphorylation; Phosphorylation; Skin diseases; Transcriptomes; allergic contact dermatitis; metabolic re-programming; keratinocytes
• ISSN: 0105-1873; 1600-0536
• DOI: 10.1111/cod.14462

Background Allergic contact dermatitis (ACD) is a common skin disease caused by the recognition of haptens by the immune system. Keratinocytes play an important role in the initiation and facilitation of inflammatory responses in ACD. Immune responses are associated with major changes in metabolism. However, metabolic re‐programming is not well studied in ACD; specifically, knowledge of metabolic alterations in structural cells is lacking. Methods Metabolic re‐programming in ACD was studied using publicly available transcriptome datasets. Primary pooled keratinocytes and a keratinocyte cell line (HaCaT) were stimulated with contact allergens, and inflammatory responses and expression of metabolic markers were measured by qPCR and flow cytometry, respectively. Results ACD is characterized by metabolic re‐programming with a metabolic profile similar to atopic dermatitis. Exposure to contact allergens causes a wide array of metabolic alterations. Stimulation of keratinocytes with contact allergens induced inflammatory responses typical for ACD and was associated with an up‐regulation of proteins representative for glucose uptake, fatty acid metabolism, oxidative phosphorylation and to some extent arginine biosynthesis. Changes in these metabolic pathways were also observed when comparing lesional with non‐lesional contact dermatitis skin. Conclusions ACD is, similarly to other inflammatory skin diseases, characterized by metabolic re‐programming. Contact allergen exposure induces expression of a wide array of metabolic pathways, which is at least in part mediated through metabolic re‐programming of keratinocytes. Allergic contact dermatitis is characterized by metabolic re‐programming (A). Contact allergen exposure induces expression of a wide array of metabolic pathways (B), which is at least in part mediated through metabolic re‐programming of keratinocytes (C).