Molecular Biology of Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease with specific genetic and immunological mechanisms. The rapid development of new techniques in molecular biology had ushered in new discoveries on the role of cytokines, chemokines, and immune cells in the pathogenesis of AD. New polymorphisms of AD are continually being reported in different populations. The physical and immunological barrier of normal intact skin is an important part of the innate immune system that protects the host against microbials and allergens that are associated with AD. Defects in the filaggrin gene FLG may play a role in facilitating exposure to allergens and microbial pathogens, which may induce Th2 polarization. Meanwhile, Th22 cells also play roles in skin barrier impairment through IL-22, and AD is often considered to be a Th2/Th22-dominant allergic disease. Mast cells and eosinophils are also involved in the inflammation via Th2 cytokines. Release of pruritogenic substances by mast cells induces scratching that further disrupts the skin barrier. Th1 and Th17 cells are mainly involved in chronic phase of AD. Keratinocytes also produce proinflammatory cytokines such as thymic stromal lymphopoietin (TSLP), which can further affect Th cells balance. The immunological characteristics of AD may differ for various endotypes and phenotypes. Due to the heterogeneity of the disease, and the redundancies of these mechanisms, our knowledge of the pathophysiology of the disease is still incomplete, which is reflected by the absence of a cure for the disease.

Molecular Mechanisms of Cutaneous Inflammatory Disorder: Atopic Dermatitis

“…IFN-γ, monocyte chemotactic protein-4, eotaxin and RANTES secreted from keratinocytes after stimulation with Th1 cytokines facilitate the migration of macrophages, eosinophils and Th1 cells into chronic AD lesions [10]. CCL26 (eotaxin-3), which is essential to eosinophil recruitment into lesional epidermis, is enhanced by IL-4 and IL-13 [186].…”

“…Genome-wide association studies (GWAS) and Immunochip analyses have identified several gene polymorphisms, susceptibility loci for AD and genetic changes caused by environmental factors that may be involved in the pathogenesis of AD. Newly-found T cells and dendritic cell (DC) subsets, cytokines, chemokines and signaling pathways have extended our understanding of the molecular pathomechanism of AD and modified the conventional concept of T helper type 1 (Th1)/T helper type 2 (Th2) imbalance paradigms [10,11,12,13]. Recent advances in the understanding of the pathomechanism of AD regarding the barrier dysfunction and immune dysregulation have led to the development of new therapeutic drugs of AD, and the efficacy and safety of these drugs are currently under the investigation.…”

Neuroendocrine cells derived chemokine vasoactive intestinal polypeptide (VIP) in allergic diseases

“…Atopic dermatitis (AD) is a type of skin inflammation and it affects 10%–20% of the population [125, 126]. Nervous system modulates the immunologic responses in the skin of AD patients.…”

The Complex Type 2 Endotype in Allergy and Asthma: From Laboratory to Bedside

“…Several endotypes can be proposed according to the inflammatory background such as Th2/IL-22/periostin high or Th17/ Th1 high or in relation to the expression of fillagrin, MATT, or vitamin D pathway gene mutations. For the Th2 type AD, serum periostin is related to disease severity [76,77].…”