title: 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.
authors.affiliation: Department of Dermatology and Venereology; University Hospital Hamburg-Eppendorf ; Hamburg, Germany.
authors.forename: J M
authors.initials: JM
authors.lastname: Brandner
authors.affiliation: Department of Dermatology and Venereology; University Hospital Hamburg-Eppendorf ; Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Zorn-Kruppa
authors.affiliation: Department of Dermatology; University of Rochester Medical Center ; Rochester, NY USA.
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Dermatology and Venereology; University Hospital Hamburg-Eppendorf ; Hamburg, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Moll
authors.affiliation: Department of Dermatology; University of Rochester Medical Center ; Rochester, NY USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Beck
authors.affiliation: Department of Dermatology; University of Rochester Medical Center ; Rochester, NY USA.
authors.forename: A
authors.initials: A
authors.lastname: De Benedetto
keywords: AD, atopic dermatitis; AMP, antimicrobial peptides; Cldn, claudin; DC, dendritic cells; FLG, filaggrin; JAM, junctional adhesion molecule; LC, Langerhans cells; MM, malignant melanoma; PRR, pattern recognition receptor; PS, psoriasis; SCC, squamous cell carcinoma; SC, stratum corneum; SG, stratum granulosum; SNP, single nucleotide polymorphism; TER, TransEpithelial Electrical Resistance; TJ, tight junction; TLR, Toll-like receptor; Th, T helper; ZO-1, zonula occludens 1; claudins; skin barrier; skin immune system; skin innate barrier; tight junction
references.citation: Ann N Y Acad Sci. 2012 Jun;1257:158-66
references.pmid: 22671602
references.citation: J Invest Dermatol. 2003 Aug;121(2):231-41
references.pmid: 12880413
references.citation: J Invest Dermatol. 2008 Sep;128(9):2248-58
references.pmid: 18385759
references.citation: J Allergy Clin Immunol. 2011 Jul;128(1):242-246.e5
references.pmid: 21489616
references.citation: J Cell Biol. 2002 Mar 18;156(6):1099-111
references.pmid: 11889141
references.citation: Curr Allergy Asthma Rep. 2004 Jul;4(4):276-84
references.pmid: 15175141
references.citation: J Cell Sci. 2010 Jun 1;123(Pt 11):1913-21
references.pmid: 20460438
references.citation: Nat Immunol. 2001 Apr;2(4):361-7
references.pmid: 11276208
references.citation: J Histochem Cytochem. 2005 May;53(5):611-9
references.pmid: 15872054
references.citation: Nat Genet. 2013 Jul;45(7):808-12
references.pmid: 23727859
references.citation: Eur J Cell Biol. 2002 Aug;81(8):419-35
references.pmid: 12234014
references.citation: Int J Clin Exp Pathol. 2013 Nov 15;6(12):2855-63
references.pmid: 24294371
references.citation: J Invest Dermatol. 2011 Mar;131(3):744-52
references.pmid: 21160495
references.citation: Arch Dermatol Res. 2001 May;293(5):239-44
references.pmid: 11409568
references.citation: Nat Cell Biol. 2007 Apr;9(4):461-9
references.pmid: 17351639
references.citation: Yonsei Med J. 2013 Mar 1;54(2):523-8
references.pmid: 23364991
references.citation: J Cutan Pathol. 2005 Sep;32(8):533-6
references.pmid: 16115050
references.citation: Science. 2001 May 11;292(5519):1102-5
references.pmid: 11352064
references.citation: J Pathol. 2007 Aug;212(4):450-8
references.pmid: 17582238
references.citation: Histopathology. 2011 Jan;58(2):286-303
references.pmid: 21323954
references.citation: J Am Acad Dermatol. 2005 Jul;53(1):52-6
references.pmid: 15965420
references.citation: Arch Dermatol Res. 2003 Sep;295(5):211-21
references.pmid: 12898148
references.citation: Immunology. 2005 Aug;115(4):565-74
references.pmid: 16011525
references.citation: Mech Dev. 2005 Jun;122(6):805-19
references.pmid: 15908185
references.citation: J Invest Dermatol. 2012 Mar;132(3 Pt 2):949-63
references.pmid: 22217737
references.citation: J Invest Dermatol. 2011 Jun;131(6):1272-9
references.pmid: 21346775
references.citation: Annu Rev Physiol. 2011;73:283-309
references.pmid: 20936941
references.citation: J Allergy Clin Immunol. 2013 Feb;131(2):266-78
references.pmid: 23374259
references.citation: J Invest Dermatol. 2010 Oct;130(10):2505-7
references.pmid: 20555350
references.citation: Cutis. 2004 Feb;73(2):115-22
references.pmid: 15027517
references.citation: J Exp Med. 2009 Dec 21;206(13):2937-46
references.pmid: 19995951
references.citation: J Cell Biol. 2005 Sep 26;170(7):1029-37
references.pmid: 16186252
references.citation: Eur J Cell Biol. 2004 Dec;83(11-12):655-65
references.pmid: 15679110
references.citation: Allergy. 2013 Jan;68(1):37-47
references.pmid: 23157658
references.citation: Eur J Cell Biol. 2007 Dec;86(11-12):645-55
references.pmid: 17291627
references.citation: FASEB J. 1996 Jun;10(8):871-81
references.pmid: 8666164
references.citation: PLoS One. 2013;8(2):e55116
references.pmid: 23390516
references.citation: Contact Dermatitis. 2010 Oct;63(4):215-22
references.pmid: 20731692
references.citation: J Am Acad Dermatol. 2001 Jul;45(1 Suppl):S29-32
references.pmid: 11423869
references.citation: J Dermatol Sci. 2013 Apr;70(1):12-8
references.pmid: 23433550
references.citation: Exp Dermatol. 2012 Mar;21(3):171-5
references.pmid: 22379962
references.citation: J Invest Dermatol. 2008 Nov;128(11):2625-30
references.pmid: 18432274
references.citation: J Dermatol. 2008 Jan;35(1):36-8
references.pmid: 18181775
references.citation: Br J Dermatol. 2013 Apr;168(4):762-70
references.pmid: 23136956
references.citation: Annu Rev Pathol. 2012;7:385-422
references.pmid: 22054142
references.citation: Exp Dermatol. 2002 Apr;11(2):159-87
references.pmid: 11994143
references.citation: Br J Dermatol. 2004 Aug;151(2):328-34
references.pmid: 15327539
references.citation: J Invest Dermatol. 2009 Jun;129(6):1339-50
references.pmid: 19322214
references.citation: Br J Dermatol. 1996 Apr;134(4):630-8
references.pmid: 8733362
references.citation: Int J Cancer. 1993 Nov 11;55(5):803-10
references.pmid: 8244578
references.citation: Mod Pathol. 2007 Sep;20(9):947-54
references.pmid: 17585317
references.citation: Curr Opin Cell Biol. 2005 Oct;17(5):453-8
references.pmid: 16098725
references.citation: J Allergy Clin Immunol. 2011 Mar;127(3):773-86.e1-7
references.pmid: 21163515
references.citation: Curr Allergy Asthma Rep. 2006 Sep;6(5):384-9
references.pmid: 16899200
references.citation: J Allergy Clin Immunol. 2009 Sep;124(3 Suppl 2):R7-R12
references.pmid: 19720210
references.citation: PLoS One. 2012;7(2):e31641
references.pmid: 22328942
references.citation: J Innate Immun. 2014;6(6):739-53
references.pmid: 24862212
references.citation: J Invest Dermatol. 2008 Apr;128(4):906-16
references.pmid: 17914452
references.citation: J Invest Dermatol. 2005 Oct;125(4):615-28
references.pmid: 16185259
references.citation: Skin Pharmacol Physiol. 2006;19(2):71-7
references.pmid: 16685145
references.citation: J Allergy Clin Immunol. 2006 Jul;118(1):3-21; quiz 22-3
references.pmid: 16815133
references.citation: Gastroenterology. 2004 Nov;127(5):1386-90
references.pmid: 15521008
references.citation: J Invest Dermatol. 2013 May;133(5):1161-9
references.pmid: 23407391
references.citation: Am J Pathol. 2012 Sep;181(3):969-77
references.pmid: 22796440
references.citation: J Invest Dermatol. 1998 Jun;110(6):862-6
references.pmid: 9620290
references.citation: J Allergy Clin Immunol. 2013 Nov;132(5):1121-9
references.pmid: 24084074
references.citation: Biochim Biophys Acta. 2009 Apr;1788(4):832-41
references.pmid: 19059200
references.citation: Cell Mol Life Sci. 2014 Sep;71(18):3599-609
references.pmid: 24573695
references.citation: Oncogene. 2007 May 31;26(26):3846-56
references.pmid: 17160014
references.citation: Nat Genet. 2006 Apr;38(4):441-6
references.pmid: 16550169
references.citation: J Gen Virol. 2003 Sep;84(Pt 9):2473-84
references.pmid: 12917468
references.citation: Nat Immunol. 2013 Oct;14(10):978-85
references.pmid: 24048119
references.citation: Am J Pathol. 2011 May;178(5):2252-63
references.pmid: 21514438
references.citation: Ann N Y Acad Sci. 2012 Jun;1257:142-51
references.pmid: 22671600
references.citation: Curr Dermatol Rep. 2013 Nov 28;3:13-22
references.pmid: 24587975
references.citation: Acta Derm Venereol. 1997 Mar;77(2):102-4
references.pmid: 9111817
references.citation: J Invest Dermatol. 1971 Jul;57(1):17-31
references.pmid: 4104141
references.citation: Skin Pharmacol Physiol. 2008;21(4):211-7
references.pmid: 18509255
references.citation: J Invest Dermatol. 2001 Nov;117(5):1050-8
references.pmid: 11710912
references.citation: J Invest Dermatol. 1983 Jun;80 Suppl:12s-16s
references.pmid: 6602189
references.citation: J Invest Dermatol. 2009 Jan;129(1):14-30
references.pmid: 19078985
references.citation: J Invest Dermatol. 2001 Sep;117(3):710-7
references.pmid: 11564181
references.citation: J Invest Dermatol. 1996 Jun;106(6):1242-9
references.pmid: 8752664
references.citation: Cold Spring Harb Perspect Biol. 2009 Aug;1(2):a002584
references.pmid: 20066090
references.citation: J Invest Dermatol. 2013 Apr;133(4):988-98
references.pmid: 23223142
references.citation: EMBO J. 2005 Mar 23;24(6):1146-56
references.pmid: 15775979
references.citation: J Cell Biol. 2010 Mar 22;188(6):935-52
references.pmid: 20308431
references.citation: J Dermatol Sci. 2013 Aug;71(2):89-99
references.pmid: 23712060
references.citation: J Invest Dermatol. 2009 Aug;129(8):1892-908
references.pmid: 19494826
references.citation: Novartis Found Symp. 2004;263:115-24; discussion 124-32, 211-8
references.pmid: 15669638
references.citation: Exp Cell Res. 2013 Oct 15;319(17):2588-603
references.pmid: 23948304
references.citation: Exp Dermatol. 2010 Oct;19(10):888-94
references.pmid: 20629740
references.citation: Eur J Cell Biol. 2002 May;81(5):253-63
references.pmid: 12067061
references.citation: J Invest Dermatol. 2011 Apr;131(4):932-43
references.pmid: 21191420
references.citation: Am J Pathol. 2005 May;166(5):1541-54
references.pmid: 15855653
references.citation: Exp Dermatol. 2012 Oct;21(10):798-801
references.pmid: 22882565
references.citation: Hum Pathol. 2008 Aug;39(8):1212-20
references.pmid: 18547615
references.citation: J Invest Dermatol. 2007 Apr;127(4):782-91
references.pmid: 17110935
references.citation: Development. 2002 Apr;129(7):1775-84
references.pmid: 11923212
references.citation: Exp Dermatol. 2007 Apr;16(4):324-30
references.pmid: 17359339
references.citation: Am J Pathol. 2009 Sep;175(3):1095-106
references.pmid: 19661441
references.citation: Eur J Cell Biol. 2010 Nov;89(11):839-42
references.pmid: 20732726
references.citation: Br J Dermatol. 2007 Mar;156(3):466-72
references.pmid: 17300235
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13610-5
references.pmid: 16157881
references.citation: J Am Acad Dermatol. 1994 Jan;30(1):35-9
references.pmid: 8277028
references.citation: Br J Dermatol. 2014 Oct;171(4):742-53
references.pmid: 24842328
references.citation: Nat Rev Microbiol. 2011 Apr;9(4):244-53
references.pmid: 21407241
references.citation: J Immunol. 2011 Sep 15;187(6):3230-7
references.pmid: 21841130
references.citation: Science. 1998 Jun 5;280(5369):1618-20
references.pmid: 9616127
references.citation: Exp Dermatol. 2012 Feb;21(2):104-10
references.pmid: 22229441
references.citation: J Invest Dermatol. 2007 Oct;127(10):2381-90
references.pmid: 17508021
references.citation: Virchows Arch. 2004 Nov;445(5):472-6
references.pmid: 15232740
references.citation: J Dermatol Sci. 2013 Aug;71(2):145-8
references.pmid: 23712061
references.citation: J Invest Dermatol. 2014 Aug;134(8):2163-73
references.pmid: 24633129
references.citation: Physiol Genomics. 2012 Apr 15;44(8):455-69
references.pmid: 22395315
references.citation: Curr Top Microbiol Immunol. 2007;315:51-66
references.pmid: 17848060
references.citation: J Invest Dermatol. 2011 Jan;131(1):150-7
references.pmid: 20861853
references.citation: Mol Biol Cell. 2009 Aug;20(16):3713-24
references.pmid: 19535456
references.citation: J Invest Dermatol. 2012 Mar;132(3 Pt 2):887-95
references.pmid: 22158560
references.citation: Gastroenterology. 2000 Jun;118(6):1001-11
references.pmid: 10833473