Molecular biology of atopic dermatitis.
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.
Department of Dermatology, Peking University People's Hospital, No11, Xizhimen South Street, Beijing, 100044, China.
Zhanglei
Z
Mu
Yan
Y
Zhao
Xiaojing
X
Liu
Christopher
C
Chang
Jianzhong
J
Zhang
D000485:Allergens / Q000276:immunology*; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D000091344:Filaggrin Proteins; D005786:Gene Expression Regulation / Q000276:immunology*; D018740:Genetic Heterogeneity; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000276:immunology*; D015603:Keratinocytes / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000276:immunology / Q000473:pathology; D012867:Skin / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology; D000097043:Interleukin-22
D000485:Allergens; D018925:Chemokines; D000091344:Filaggrin Proteins; D007378:Interleukins; D007381:Intermediate Filament Proteins; D000097043:Interleukin-22; C000717249:FLG protein, human