Fc Epsilon RI-Neuroimmune Interplay in Pruritus Triggered by Particulate Matter in Atopic Dermatitis Patients.

ABSTRACT

Atopic dermatitis (AD) is the most common chronic relapsing neuroinflammatory skin disease that is characterized by a complex and multifactorial pathophysiology. It reflects a profound interplay between genetic and environmental factors, and a recently disclosed neuroimmune dysregulation that drives skin barrier disruption, pruritus, and microbial imbalance. In terms of the key external environmental players that impact AD, air quality and itch severity linkage have been thoroughly researched. The impact of ambient air pollutants including particulate matter (PM) and AD pruritic exacerbation has been recorded despite reductions in air pollution levels in in developed countries. The developing countries have, on the contrary, experienced significant urbanization and industrialization with limited environmental protection standards in the past decades. This unprecedented construction, petrochemical industry utilization, and increment in population counts has been paired with consistent exposure to outdoor PM. This may present a key cause of AD pruritic exacerbation supported by the fact that AD prevalence has intensified globally in the past 50 years, indicating that environmental exposure may act as a trigger that could flare up itch in vulnerable persons. At the molecular level, the impact of PM on severe pruritus in AD could be interpreted by the toxic effects on the complex neuroimmune pathways that govern this disease. AD has been recently viewed as a manifestation of the disruption of both the immune and neurological systems. In light of these facts, this current review aims to introduce the basic concepts of itch sensory circuits in the neuroimmune system. In addition, it describes the impact of PM on the potential neuroimmune pathways in AD pathogenesis with a special focus on the Fc Epsilon RI pathway. Finally, the review proposes potential treatment lines that could be targeted to alleviate pruritus based on immune mediators involved in the Fc Epsilon signaling map.