Epidermal tight junctions in health and disease

Abstract

The skin, the largest organ of the body, is an essential barrier that under homeostatic conditions efficiently protects and/or minimizes damage from both environmental (e.g. microorganisms, physical trauma, ultraviolet radiation) and endogenous (e.g., cancers, inflammation) factors. This formidable barrier function resides mainly in the epidermis, a dynamic, highly-stratified epithelium. The epidermis has 2 major barrier structures: stratum corneum, the outmost layer and tight junctions, intercellular junctions that seal adjacent keratinocytes in the stratum granulosum, found below the stratum corneum.

In recent years there have been significant advances in our understanding of tight junction function, composition and regulation. Herein we review what is known about tight junctions in healthy skin and keratinocyte culture systems and highlight the dynamic crosstalk observed between tight junctions and the cutaneous immune system. Finally we discuss the preliminary observations suggesting that tight junction function or protein expression may be relevant for the pathogenesis of a number of common cutaneous inflammatory and neoplastic conditions.

Keywords:

• claudins
• skin barrier
• skin innate barrier
• skin immune system
• tight junction

Abbreviations:

• AD, atopic dermatitis
• AMP, antimicrobial peptides
• Cldn, claudin
• DC, dendritic cells
• FLG, filaggrin
• JAM, junctional adhesion molecule
• LC, Langerhans cells
• MM, malignant melanoma
• PS, psoriasis
• SCC, squamous cell carcinoma; SC, stratum corneum
• SG, stratum granulosum
• SNP, single nucleotide polymorphism
• PRR, pattern recognition receptor
• Th, T helper
• TJ, tight junction
• TER, TransEpithelial Electrical Resistance
• TLR, Toll-like receptor
• ZO-1, zonula occludens 1

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Funding

The authors recognized the following funding sources: Deutsche Forschungsgemeinschaft (FOR 721/2, BR 1982-4-1 JMB); Atopic Dermatitis Research Network (NIAID subcontract HHSN272201000020C and HHSN272201000017C; L.A.B), NIH/NIAMS R21 (AR062357; L.A.B.); Dermatology Foundation (A.D.B.) and University of Rochester Medical Center (A.D.B).