Abstract
Allergic contact dermatitis is a common occupational disease that manifests as a cell-mediated hypersensitivity reaction following skin exposure to small reactive chemicals termed haptens. Haptens penetrate the stratum corneum and covalently modify proteins in the epidermis, inducing intracellular stress, which further leads to the release of damage-associated molecular patterns (DAMPs), such as uric acid, reactive oxygen species, hyaluronic acid fragments and extracellular adenosine triphosphate (ATP). These DAMPs are recognized by pattern recognition receptors (PRRs) in innate immune cells, namely dendritic cells (DCs), leading to their maturation and migration to the draining lymph nodes where they activate naïve T lymphocytes. Among all PRRs, several studies emphasize the role of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome on the allergic contact dermatitis (ACD) sensitization phase. However, skin allergens—danger signals—NLRP3 inflammasome axis is yet to be completely elucidated. Therefore, in this review, we sought to discuss the molecular mechanisms underlying DAMPs release and NLRP3 inflammasome activation triggered by skin allergens. The elucidation of these key events might help to identify novel therapeutic strategies for ACD, as well as the development of nonanimal alternative methods for the identification and potency categorization of skin sensitizers.
Highlights
Allergic contact dermatitis (ACD) is one of the most common occupational diseases, affecting nearly 20% of the European population [1,2,3]
Studies addressing the role of cardiolipin in ACD remain limited, we previously reported that THP-1 cells treated with the skin sensitizer DNFB showed a striking increase in cardiolipins and that their remodeling may be an important mechanism by which allergens cause redox imbalance [74]
It is well known that allergens trigger inflammation as well as the release of damage-associated molecular patterns (DAMPs), which can promote the NLRP3 inflammasome activation and IL-1β secretion
Summary
Allergic contact dermatitis (ACD) is one of the most common occupational diseases, affecting nearly 20% of the European population [1,2,3]. In germ-free mice, exposure to contact allergens leads to the activation of PRRs involved in anti-microbial defense, suggesting that endogenous DAMPs play an important role in the development of ACD. These danger signals are capable of activating various cell types from both innate and adaptive immune responses [15]. Inflammasomes are cytosolic multiprotein signaling platforms that assemble in the presence of pathogenic microorganisms and sterile stressors and are involved in the control of the inflammatory response and coordination of antimicrobial host defense [19] They are responsible for mediating caspase-1 activation (which promotes the secretion of the proinflammatory cytokines interleukin (IL)-1β and IL-18) as well as pyroptosis, a form of cell death induced by bacterial pathogens [20]. A deeper understanding of these events might help to define novel therapeutic strategies for ACD and to design novel nonanimal in vitro tests for the identification of sensitizers
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