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

Affiliations
  • 1Medical Corps of Sangmudae Army Service Support Group, Republic of Korea Army Training and Doctrine Command, Jangsung, Korea.
  • 2Department of Dermatology, Gangnam Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea. ydshderm@yuhs.ac

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.


Cited by  3 articles

Personalized Immunomodulatory Therapy for Atopic Dermatitis: An Allergist's View
Dong-Ho Nahm
Ann Dermatol. 2015;27(4):355-363.    doi: 10.5021/ad.2015.27.4.355.

Consensus Guidelines for the Treatment of Atopic Dermatitis in Korea (Part I): General Management and Topical Treatment
Jung Eun Kim, Hyun Jeong Kim, Bark-Lynn Lew, Kyung Ho Lee, Seung Phil Hong, Yong Hyun Jang, Kui Young Park, Seong Jun Seo, Jung Min Bae, Eung Ho Choi, Ki Beom Suhr, Seung Chul Lee, Hyun Chang Ko, Young Lip Park, Sang Wook Son, Young Jun Seo, Yang Won Lee, Sang Hyun Cho, Chun Wook Park, Joo Young Roh
Ann Dermatol. 2015;27(5):563-577.    doi: 10.5021/ad.2015.27.5.563.

Significance of Skin Barrier Dysfunction in Atopic Dermatitis
Byung Eui Kim, Donald Y.M. Leung
Allergy Asthma Immunol Res. 2018;10(3):207-215.    doi: 10.4168/aair.2018.10.3.207.


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