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Cell and Tissue Research

, Volume 360, Issue 3, pp 723–748 | Cite as

Hereditary barrier-related diseases involving the tight junction: lessons from skin and intestine

  • Johanna M. BrandnerEmail author
  • Jörg D. SchulzkeEmail author
Review

Abstract

The tight junction (TJ) regulates paracellular barrier properties. TJs are composed of transmembrane proteins, i.e., claudins, occludin, tricellulin and junctional adhesion molecules as well as TJ plaque proteins. Their relative abundance and composition determines epithelial tightness. TJs undergo rapid regulation by various signalling pathways, either directly addressing TJ transmembrane proteins or via plaque proteins and the cytoskeleton. In the skin, TJs exert predominantly barrier functions, while in the intestine they also mediate paracellular ion and water transport. In diseases, TJs can either be primarily affected (hereditary TJ defects) or changes can result from secondary regulatory inputs as, e.g., in inflammatory diseases (secondary TJ defects). Secondary TJ defects can maintain disease activity, e.g., by enhanced antigen leak. This review discusses TJ composition, function and regulation as well as primary and secondary tight junction defects in a comparative manner in skin and intestine in order to elucidate similarities and differences.

Keywords

Tight junctions Claudins Occludin JAMs NISCH syndrome Atopic dermatitis Crohn’s disease 

Abbreviations

AD

Atopic dermatitis

DD

Darier’s disease

DHD

Dermatitis herpetiformis Duhring

EM

Electron microscopy

HHD

Hailey Hailey disease

IBD

Inflammatory bowel disease

JAM

Junctional adhesion molecule

NISCH

Neonatal ichthyosis sclerosing cholangitis

TAMP

Tight junction-associated Marvel proteins

RHS

Reconstructed human skin

SB

Stratum basale

SC

Stratum corneum

SG

Stratum granulousm

SS

Stratum spinosum

TJ

Tight junction

ZO

Zonula occludens

Notes

Acknowledgments

The authors are grateful to Michael Fromm, Dorothee Günzel and Michaela Zorn-Kruppa for critically reading the manuscript and for valuable discussions. This work was supported by the Deutsche Forschungsgemeinschaft (FOR 721/2 TP 9 and BR1982/4-1 to J.M.B. and FOR 721/2 TP 2 to J.D.S.).

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© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of Dermatology and VenerologyUniversity Hospital Hamburg-EppendorfHamburgGermany
  2. 2.Institute of Clinical Physiology, Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin FranklinCharité – Universitätsmedizin BerlinBerlinGermany

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