Abstract
Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, which generally presents with intense itching and recurrent eczematous lesions. AD affects up to 20% of children and 10% of adults in high-income countries. The prevalence and incidence of AD have increased in recent years. The onset of AD mostly occurs in childhood, although in some cases AD may persist in adult life or even manifest in middle age (adult-onset AD). AD pathophysiology is made of a complex net, in which genetic background, skin barrier dysfunction, innate and adaptive immune responses, as well as itch contribute to disease development, progression, and chronicization. One of the most important features of AD is skin dehydration, which is mainly caused by filaggrin mutations that determine trans-epidermal water loss, pH alterations, and antigen penetration. In accordance with the “outside-inside” theory of AD pathogenesis, in a context of an altered epidermal barrier, antigens encounter epidermal antigen presentation cells (APCs), such as epidermal Langerhans cells and inflammatory epidermal dendritic cells, leading to their maturation and Th-2 cell-mediated inflammation. APCs also bear trimeric high-affinity receptors for immunoglobulin E (IgE), which induce IgE-mediated sensitizations as part of pathogenic mechanisms leading to AD. In this review, we discuss the role of cytokines in the pathogenesis of AD, considering patients with various clinical AD phenotypes. Moreover, we describe the cytokine patterns in patients with AD at different phases of the disease evolution, as well as in relation to different phenotypes/endotypes, including age, race, and intrinsic/extrinsic subtypes. We also discuss the outcomes of current biologics for AD, which corroborate the presence of multiple cytokine axes involved in the background of AD. A deep insight into the correlation between cytokine patterns and the related clinical forms of AD is a crucial step towards increasingly personalized, and therefore more efficient therapy.
Highlights
Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, characterized by intense itching and recurrent eczematous lesions [1]
AD pathophysiology is made of a complex net, in which genetic background, skin barrier dysfunction, innate and adaptive immune responses, and itch contribute to development, progression, and chronicitation of disease [3]
Shao et al demonstrated that the serine-threonine kinase IRAK2 is the main intracellular effector of IL-36 and IL-1 cytokines in human keratinocytes, and its levels correlate with disease severity in AD and psoriasis [53] (Figure 1)
Summary
Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, characterized by intense itching and recurrent eczematous lesions [1]. AD pathophysiology is made of a complex net, in which genetic background, skin barrier dysfunction, innate and adaptive immune responses, and itch contribute to development, progression, and chronicitation of disease [3]. Th2-derived cytokines, together with inflammatory mediators released by innate immune cells, such as mast cells, pathogenically contribute to the initiation and amplification of skin inflammation in AD lesions. 2022, 23, 2684 indicates that FLG-deficiency renders skin equivalents more sensitive to the detrimental effects of IL-4 and IL-13 compared to skin equivalents with normal FLG expression, and defects in the epidermal barrier, skin permeability, and cutaneous innate immune response are not primarily linked to FLG gene deficiency but are rather secondarily induced by Th2 inflammation [15] Sci. 2022, 23, 2684 indicates that FLG-deficiency renders skin equivalents more sensitive to the detrimental effects of IL-4 and IL-13 compared to skin equivalents with normal FLG expression, and defects in the epidermal barrier, skin permeability, and cutaneous innate immune response are not primarily linked to FLG gene deficiency but are rather secondarily induced by Th2 inflammation [15]
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