CCL2-CCR2 signaling in the skin drives surfactant-induced irritant contact dermatitis via IL-1β-mediated neutrophil accumulation
Irritant contact dermatitis (ICD) is a common skin disorder caused by exposure to
chemicals with irritant properties (Gittler et al. 2013). ICD can develop after a single
overwhelming exposure to an irritant (acute ICD); however, it is often caused by
multiple subthreshold insults induced by weak irritants, such as surfactants contained
in soaps, shampoos, and detergents (cumulative ICD) (Slodownik et al. 2008). This
disorder is characterized by skin inflammation and skin barrier disruption with immune
cell infiltration and, in the case of the cumulative type, epidermal hyperplasia (Cohen,
E. 2018). ICD is the most common form of occupational skin disorder and leads to an
impaired quality of life and reduced productivity (Dickel et al. 2002; Dietz et al. 2020).
In addition, exposure to irritants could be involved in both the development and
aggravation of atopic dermatitis (Akdis et al. 2006; Williams et al. 2007). Thus, it is
essential to manage ICD based on an understanding of its pathogenesis.
The release of soluble mediators from skin cells (principally keratinocytes)
damaged by irritants induces an inflammatory cytokine/chemokine milieu with
immune cell accumulation, leading to the development of ICD (Gittler et al. 2013;
Slodownik et al. 2008). However, the roles of only limited cytokines (TNF-α, IL-6,
and IL-10) in ICD have been evaluated in vivo (Berg et al. 1995; Lee et al. 2013;
Piguet 1991). As for immune cells, accumulation of neutrophils and lymphocytes in
the lesional skin of human ICD has been described, although patterns of immune cell
infiltration have not been well investigated (Weedon 2010). ...