Allergy Asthma Immunol Res.  2014 Jul;6(4):276-287. 10.4168/aair.2014.6.4.276.

Epidermal Permeability Barrier Defects and Barrier Repair Therapy in Atopic Dermatitis

• Lee HJ
• Lee SH

• KMID: 2260207
• DOI: http://doi.org/10.4168/aair.2014.6.4.276

Abstract

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease perpetuated by gene-environmental interactions and which is characterized by genetic barrier defects and allergic inflammation. Recent studies demonstrate an important role for the epidermal permeability barrier in AD that is closely related to chronic immune activation in the skin during systemic allergic reactions. Moreover, acquired stressors (e.g., Staphylococcus aureus infection) to the skin barrier may also initiate inflammation in AD. Many studies involving patients with AD revealed that defective skin barriers combined with abnormal immune responses might contribute to the pathophysiology of AD, supporting the outside-inside hypothesis. In this review, we discuss the recent advances in human and animal models, focusing on the defects of the epidermal permeability barrier, its immunologic role and barrier repair therapy in AD.

Keyword

Atopic dermatitis; barrier repair therapy; skin barrier

MeSH Terms

Dermatitis, Atopic*
Humans
Hypersensitivity
Inflammation
Models, Animal
Permeability*
Skin
Skin Diseases
Staphylococcus aureus

Figure

• 

  Fig. 1 Barrier dysfunction associated with filaggrin deficiency leads to lipid bilayer disorganization, delayed bilayer maturation, as well as decreased SC cohesion, paracellular permeability barrier, and photoprotection, which all may play important roles in the pathogenesis of atopic dermatitis (AD). NMF, natural moisturizing factors; SC, stratum corneum; TEWL, transepidermal water loss.

• 

  Fig. 2 The factors involved in acidic pH maintenance and their role in normal epidermis, and the consequences of altered pH in patients with AD. (A) Exogenous free fatty acids are derived from sweat glands or catalyzed from sebaceous gland-derived triglycerol moieties via microorganism-secreted lipases. Endogenous free fatty acids are derived from phospholipids by phospholipase A2 (PLA2), both of which are secreted by lamellar bodies (LBs) at the SC-stratum granulosum junction. Additionally, the Na+/H+ antiporter is involved in maintaining the skin acid mantle. Therefore, the skin acid mantle regulates SC integrity and cohesion, antimicrobial function, processing of LB polar lipids, structural organization of lamellar membrane, and β-glucocerebrosidase/sphingomyelinase function. (B) AD or other stressors alter the function of the skin acid mantle. The altered acid mantle increases serine protease activity and decreases the function of corneodesmosomes, resulting in decreased production of ceramides and LB secretion, altered SC cohesion and inflammation activation.

• 

  Fig. 3 The roles of serine protease and PAR-2 in AD. AMP, antimicrobial peptide; FLG, filaggrin; KLK, kallikrein; LB, lamellar body; LEKTI, lymphoepithelial Kazal-type-related inhibitor; LTN, lipoglycan; PAR-2, protease activated receptor-2; PGN, peptidoglycan; TLR, toll-like receptor; TSLP, thymic stromal lymphopoietin.

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