Track: Basic Science

Topic: Inflammatory Diseases

Abstract:

Iron is an essential nutrient utilized by all cells of the human body for redox metabolic processes. Iron homeostasis is maintained by multiple physiologic mechanisms. Recent studies have identified a critical role for the epidermis in the regulation of iron homeostasis through high-capacity ferritin iron storage and desquamation. Iron is sequestered by various inflammatory stimuli as a protective host mechanism due to its importance for pathogen survival. Systemic inflammation drives hepcidin-dependent iron sequestration in the pathogenic mechanism underlying anemia of chronic disease. In contrast, skin inflammation directly drives epidermal iron sequestration, resulting in epidermal iron loss and true iron deficiency in a phenomena termed “anemia of skin disease.” Mechanisms driving inflammatory epidermal iron sequestration have yet to be investigated. The purpose of this study was to characterize epidermal iron sequestration in human inflammatory skin disease. We utilized immunofluorescence to identify the distribution of ferritin in the epidermis in psoriasis. Two separate anti-ferritin-chain antibodies were used to stain normal versus lesional psoriasis skin. Diffuse distribution of both chains was observed throughout the epidermis in non-lesional skin. Lesional skin demonstrated proportional increases in ferritin expression throughout the epidermis. To investigate mechanisms of epidermal iron accumulation we further assessed changes in the abundance of ferroportin, a major iron export channel expressed by human keratinocytes. Inflammation drove decreased ferroportin expression, consistent with the observation of increased ferritin with epidermal inflammation. These findings suggest that the epidermis directly sequesters iron as a function of inflammation by keratinocyte-autonomous modulation of ferroportin expression.

Keywords: Inflammatory: Psoriasiform,Other: Immunofluorescence

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ASDP 60th Annual Meeting

Epidermal Ferritin Expression in Inflammatory Skin Disease