As skin barrier function decreases, allergen stimulation is believed to result in the release of thymic stromal lymphopoietin (TSLP), which stimulates dendritic cells to promote a Th2-driven immune response by promoting differentiation of naïve T cells into Th2 cells (Yoo et al., 2005; Oyoshi et al., 2010; Novak, 2012). As the inflammatory pathway progresses, an increased infiltration of T cells, dendritic cell subtypes, macrophages, mast cells and eosinophils within the skin is observed (Boguniewicz & Leung, 2011; Novak, 2012). Patients with atopic dermatitis have a genetically determined dominance of Th2 lymphocytes (Bieber, 2008) and this translates into increased levels of the Th2 cytokines IL-4, IL-13, IL-25 and IL-33 (Peng & Novak, 2015).
The key cytokines within a Th2-driven immune response are IL-4 and IL-13. Both cytokines signal via the IL-4 receptor α (IL-4Rα) to promote IgE production by B cells, dendritic cell differentiation, activation of T cells and recruitment of eosinophils (Peng & Novak, 2015). Interestingly, the immune cells that infiltrate the skin of atopic dermatitis patients might behave differently to those seen in individuals without the condition. Activation of Toll-like receptor 2 (TLR2) on monocytes and macrophages from patients with atopic dermatitis resulted in a different cytokine and chemokine response compared to those from healthy controls (Niebuhr et al., 2008; Niebuhr et al., 2009; Kuo et al., 2013).
Mast cells also play an important role in the inflammatory response as well as being key mediators of type 1 hypersensitivity. The number of mast cells is elevated in the skin lesions of patients with atopic dermatitis and it has been suggested that they promote skin inflammation in this setting through the release of IL-31 (Otsuka & Kabashima, 2015). Furthermore, they have been shown to degranulate and release proinflammatory mediators following stimulation by δ toxin released by S. aureus (Nakamura et al., 2013).
As atopic dermatitis progresses towards a chronic state, the underlying inflammatory response changes and shifts from predominantly Th2-driven inflammation to mixed Th2/Th1/Th17/Th22 response. The consequences of this change are greater keratinocyte apoptosis due to Th1-mediated release of IFN-γ and tissue remodelling, increased skin thickness and lichenification as a result of Th22 cell activation (Peng & Novak, 2015).