Skin immunity and its dysregulation in atopic dermatitis, hidradenitis suppurativa and vitiligo

Abstract

While the epidermis is the frontline defense against infections and indeed, it is a peripheral lymphoid organ, the same immunological mechanisms may initiate and sustain pathological conditions. Indeed, a deregulated action against exogenous pathogens could activate a T cell response in atopic dermatitis, hidradenitis suppurativa and vitiligo. Atopic dermatitis (AD) is a chronic inflammatory skin condition with a complex pathophysiology. Although T helper 2 immunity dysregulation is thought to be the main cause of AD etiopathogenesis, the triggering mechanism is not well understood, and the treatment is often difficult. As the AD, hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a dramatic impact on the quality of life of the affected patients. The exact pathophysiology of HS is still unclear, but many evidences report a follicular obstruction and subsequent inflammation with TNF-α, interleukin (IL)-1β, IL-10, and IL-17 involvement. Vitiligo is an autoimmune epidermal disorder which consists of melanocytes destruction and skin depigmentation. Melanocytes destruction is mainly due to their increased oxidative-stress sensitivity with a consequent activation of innate first and adaptative immunity (CD8⁺ T cells) later. The understanding of the triggering mechanisms of AD, HS and Vitiligo is pivotal to outline novel therapies aimed at regaining the physiological immune homeostasis of healthy skin. The aim of this review is to provide new insight on the pathogenesis of these skin diseases and to highlight on the new therapeutic approaches adopted in the treatment of AD, HS and Vitiligo.

Keywords: Atopic dermatitis; hidradenitis suppurativa; vitiligo.

Figure 1.

Immunopathogenesis of AD. The genetic impairment of skin barrier increases allergens and microbial pathogens penetration into the skin. The allergens induce IgE production by B cells, and the complex IgE-allergens activates the DCs and mast cells. The activation of DCs induces the Th2 polarization. The main Th2 cytokines, IL-4, IL-5, and IL-13 may downregulate the expression of TLRs and AMPs in keratinocytes, exacerbating the disease. Th22 lymphocytes producing Il-22 and Th1 and Th17 mainly via IFN-γ and IL-17 play a role in skin inflammation especially in the chronic stage of AD. Pruritus can be caused by mast cells producing histamine, tryptase, and other inflammatory mediators. Mast cells can exacerbate AD-producing IL-4 and IL-13. IL-5 activates eosinophils. Pruritus may induce scratching which also damages the skin barrier and increases TEWL, which induces skin dryness exacerbating AD.

Figure 2.

Immunopathogenesis of HS. In a background of smoking habitus and obesity, the interaction between γ-secretase mutation, bacteria and follicular obstruction can allow the inflammasome activation mediated by Th1/Th17 axis and their cytokines.

Figure 3.

Immunopathogenesis of vitiligo. In predisposed patients (due to exogenous triggers and genetic predisposition), abnormal melanocytes induce the release of inflammatory cytokines which contribute to activation of the innate immune response and subsequently to adaptive T cell responses, producing TNFα and IFNγ involved in melanocyte loss and development of white patches.