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


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.


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



Atopic dermatitis


Darier’s disease


Dermatitis herpetiformis Duhring


Electron microscopy


Hailey Hailey disease


Inflammatory bowel disease


Junctional adhesion molecule


Neonatal ichthyosis sclerosing cholangitis


Tight junction-associated Marvel proteins


Reconstructed human skin


Stratum basale


Stratum corneum


Stratum granulousm


Stratum spinosum


Tight junction


Zonula occludens



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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