title: The chemokine receptor CCR7 expressed by dendritic cells: a key player in corneal and ocular surface inflammation.
abstract: Dendritic cells (DCs) are highly potent stimulators of the immune system, and their contribution as such to the pathogenesis of corneal and ocular surface inflammatory disease has been well established. These vigorous antigen-presenting cells are reliant upon their effective migration from peripheral tissues (e.g., those of the ocular surface) to the lymphoid organs, where immune responses are triggered and can then cause disease. The chemokine receptor CCR7 expressed on DCs has emerged as the master mediator of this highly complex migratory process, and thus it is important in causing corneal and ocular surface inflammation. Furthermore, CCR7 has received considerable attention as a potential therapeutic target, as topically instilled antagonists of this receptor are quite effective therapeutically in a mouse model of ocular allergy. These findings and more are reviewed in the current article. In addition, the understanding regarding CCR7 function in mice and humans, and the biology of DCs that populate the ocular surface are also detailed herein. The involvement of DCs and their expression of CCR7 in corneal and ocular surface diseases such as in ocular allergy, dry eye disease, immune rejection and more, are also reviewed here.
authors.affiliation: Department of Ophthalmology, Duke University School of Medicine, Durham, NC, USA; Department of Immunology, Duke University School of Medicine, Durham, NC, USA. Electronic address: daniel.saban@duke.edu.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Saban
mesh_terms: D000818:Animals; D003231:Conjunctivitis / Q000276:immunology* / Q000473:pathology; D003315:Cornea / Q000166:cytology / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007634:Keratitis / Q000276:immunology* / Q000473:pathology; D054400:Receptors, CCR7 / Q000276:immunology*
chemical_list: C515370:CCR7 protein, human; C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7
keywords: CCR7; CD103; T cells; allergic conjunctivitis; conjunctivitis; dendritic cells; dry eye disease; keratitis; ocular allergy; ocular surface
references.citation: J Immunol. 1997 Dec 1;159(11):5671-9
references.pmid: 9548511
references.citation: Immunity. 2009 Sep 18;31(3):513-25
references.pmid: 19733489
references.citation: Br J Ophthalmol. 2000 Oct;84(10):1191-3
references.pmid: 11004109
references.citation: J Immunol. 2009 Feb 1;182(3):1247-52
references.pmid: 19155469
references.citation: Curr Eye Res. 2013 Mar;38(3):317-30
references.pmid: 23281793
references.citation: J Leukoc Biol. 2013 Aug;94(2):343-51
references.pmid: 23695308
references.citation: Blood. 2005 Jul 15;106(2):444-6
references.pmid: 15863780
references.citation: Mol Vis. 2007 Apr 27;13:626-34
references.pmid: 17515886
references.citation: Ocul Surf. 2009 Apr;7(2):67-77
references.pmid: 19383275
references.citation: Exp Mol Pathol. 2007 Oct;83(2):216-23
references.pmid: 17560570
references.citation: Invest Ophthalmol Vis Sci. 2002 Mar;43(3):639-46
references.pmid: 11867578
references.citation: Invest Ophthalmol Vis Sci. 2012 Aug 17;53(9):5632-40
references.pmid: 22789921
references.citation: Eur J Immunol. 1999 May;29(5):1617-25
references.pmid: 10359116
references.citation: J Exp Med. 1998 Jul 6;188(1):181-91
references.pmid: 9653094
references.citation: J Immunol. 2006 Apr 1;176(7):3950-7
references.pmid: 16547229
references.citation: Mol Vis. 2007 Nov 28;13:2209-13
references.pmid: 18087238
references.citation: J Exp Med. 2010 Apr 12;207(4):823-36
references.pmid: 20351058
references.citation: Int J Hematol. 2002 Apr;75(3):332-4
references.pmid: 11999366
references.citation: J Clin Pathol. 2005 Oct;58(10):1057-63
references.pmid: 16189151
references.citation: Invest Ophthalmol Vis Sci. 2010 Feb;51(2):816-21
references.pmid: 19797201
references.citation: Immunity. 2013 May 23;38(5):958-69
references.pmid: 23664832
references.citation: J Biol Chem. 1997 Aug 1;272(31):19518-24
references.pmid: 9235955
references.citation: J Virol. 1993 Apr;67(4):2209-20
references.pmid: 8383238
references.citation: Cell. 1999 Oct 1;99(1):23-33
references.pmid: 10520991
references.citation: Graefes Arch Clin Exp Ophthalmol. 2006 Oct;244(10):1240-5
references.pmid: 16538446
references.citation: PLoS One. 2013 Sep 23;8(9):e75937
references.pmid: 24086667
references.citation: Nature. 1999 Oct 14;401(6754):708-12
references.pmid: 10537110
references.citation: Immunity. 2004 Aug;21(2):279-88
references.pmid: 15308107
references.citation: J Biol Chem. 1997 May 23;272(21):13803-9
references.pmid: 9153236
references.citation: Immunity. 2013 May 23;38(5):970-83
references.pmid: 23706669
references.citation: J Immunol. 2005 Feb 1;174(3):1693-700
references.pmid: 15661933
references.citation: J Leukoc Biol. 2012 Apr;91(4):621-7
references.pmid: 22291211
references.citation: Genomics. 1994 Oct;23(3):643-50
references.pmid: 7851893
references.citation: Nat Rev Immunol. 2008 May;8(5):362-71
references.pmid: 18379575
references.citation: J Immunol. 2011 Oct 1;187(7):3653-62
references.pmid: 21880984
references.citation: Invest Ophthalmol Vis Sci. 2010 Jan;51(1):344-54
references.pmid: 19737877
references.citation: J Immunol. 1997 Aug 15;159(4):1589-93
references.pmid: 9257816
references.citation: J Exp Med. 2007 Dec 24;204(13):3147-56
references.pmid: 18086865
references.citation: Am J Pathol. 2011 Oct;179(4):1807-14
references.pmid: 21843497
references.citation: Nat Immunol. 2007 Nov;8(11):1255-65
references.pmid: 17893676
references.citation: J Immunol. 2001 Jan 1;166(1):361-9
references.pmid: 11123313
references.citation: Curr Opin Allergy Clin Immunol. 2005 Oct;5(5):446-50
references.pmid: 16131922
references.citation: J Immunol. 2007 Jun 1;178(11):6861-6
references.pmid: 17513734
references.citation: Int Rev Immunol. 2013 Feb;32(1):19-41
references.pmid: 23360156
references.citation: J Exp Med. 2009 Dec 21;206(13):3115-30
references.pmid: 20008528
references.citation: J Exp Med. 2003 Aug 18;198(4):615-21
references.pmid: 12925677
references.citation: Nat Med. 2004 Aug;10(8):813-5
references.pmid: 15235599
references.citation: PLoS One. 2013 May 14;8(5):e64193
references.pmid: 23691170
references.citation: J Immunol. 2008 Jul 15;181(2):1190-8
references.pmid: 18606672
references.citation: Am J Pathol. 2012 Jun;180(6):2351-60
references.pmid: 22507838
references.citation: Biochem Biophys Res Commun. 1995 Oct 13;215(2):737-43
references.pmid: 7488016
references.citation: Trends Cardiovasc Med. 2011 Nov;21(8):211-6
references.pmid: 22902067
references.citation: Invest Ophthalmol Vis Sci. 2007 Oct;48(10):4459-67
references.pmid: 17898266
references.citation: Arch Ophthalmol. 2012 Jan;130(1):84-9
references.pmid: 21911653
references.citation: J Leukoc Biol. 2003 Aug;74(2):172-8
references.pmid: 12885933
references.citation: Immunology. 2008 Dec;125(4):541-8
references.pmid: 18540963
references.citation: Invest Ophthalmol Vis Sci. 2013 Jun 12;54(6):4081-91
references.pmid: 23702781
references.citation: J Immunol. 1998 Sep 15;161(6):3096-102
references.pmid: 9743376
references.citation: Am J Pathol. 2009 Sep;175(3):1136-47
references.pmid: 19700744
references.citation: Invest Ophthalmol Vis Sci. 2002 Jul;43(7):2264-71
references.pmid: 12091426
references.citation: Blood. 2002 Aug 15;100(4):1354-61
references.pmid: 12149218
references.citation: Invest Ophthalmol Vis Sci. 2012 Apr 24;53(4):2062-75
references.pmid: 22395876
references.citation: Invest Ophthalmol Vis Sci. 2011 Jun 28;52(7):4598-604
references.pmid: 21482644
references.citation: Invest Ophthalmol Vis Sci. 2009 Aug;50(8):3802-7
references.pmid: 19339740
references.citation: J Immunol. 1999 Mar 1;162(5):2472-5
references.pmid: 10072485
references.citation: Am J Pathol. 2011 Nov;179(5):2243-53
references.pmid: 21924232
references.citation: Curr Eye Res. 2012 Nov;37(11):1012-8
references.pmid: 22667765
references.citation: Nat Rev Immunol. 2008 Dec;8(12):935-47
references.pmid: 19029989
references.citation: Am J Pathol. 2010 Aug;177(2):744-53
references.pmid: 20566743
references.citation: Ophthalmology. 1993 Mar;100(3):339-46
references.pmid: 8460003
references.citation: J Exp Med. 1999 Feb 1;189(3):451-60
references.pmid: 9927507
references.citation: Nat Immunol. 2009 May;10(5):488-95
references.pmid: 19349986
references.citation: J Biol Chem. 1998 Mar 20;273(12):7118-22
references.pmid: 9507024
references.citation: J Allergy Clin Immunol. 1997 Dec;100(6 Pt 1):817-24
references.pmid: 9438492
references.citation: J Immunol. 2007 Mar 1;178(5):3288-92
references.pmid: 17312179
references.citation: Invest Ophthalmol Vis Sci. 2003 Feb;44(2):581-9
references.pmid: 12556386
references.citation: J Immunol. 2012 Feb 1;188(3):1350-9
references.pmid: 22210909
references.citation: J Immunol. 2004 Oct 1;173(7):4464-9
references.pmid: 15383577
references.citation: J Exp Med. 1998 Jul 20;188(2):373-86
references.pmid: 9670049
references.citation: J Exp Med. 2003 Sep 1;198(5):715-24
references.pmid: 12953093
references.citation: Eur J Immunol. 2010 Aug;40(8):2085-8
references.pmid: 20853490
references.citation: Invest Ophthalmol Vis Sci. 2010 Jul;51(7):3418-23
references.pmid: 20019373
references.citation: Invest Ophthalmol Vis Sci. 2002 Aug;43(8):2609-14
references.pmid: 12147592
references.citation: J Immunol. 1997 Feb 1;158(3):1033-6
references.pmid: 9013939
references.citation: Virol J. 2004 Sep 23;1:5
references.pmid: 15507126
references.citation: Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12694-9
references.pmid: 11070085
references.citation: Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):258-63
references.pmid: 9419363
references.citation: Mucosal Immunol. 2014 Jan;7(1):38-45
references.pmid: 23571503
references.citation: Trends Immunol. 2013 Sep;34(9):440-5
references.pmid: 23831267
references.citation: J Immunol. 1997 Sep 15;159(6):2554-8
references.pmid: 9300671
references.citation: Int Rev Immunol. 2013 Feb;32(1):57-67
references.pmid: 23360158
references.citation: Science. 2002 Jun 7;296(5574):1873-6
references.pmid: 12052961
references.citation: J Exp Med. 2001 Jan 15;193(2):207-18
references.pmid: 11148224
references.citation: J Immunol. 2010 Oct 15;185(8):4691-7
references.pmid: 20844200
references.citation: J Exp Med. 2007 Apr 16;204(4):735-45
references.pmid: 17371928
references.citation: J Exp Med. 2001 May 7;193(9):1105-12
references.pmid: 11342595
references.citation: J Exp Med. 1999 Oct 18;190(8):1183-8
references.pmid: 10523616
references.citation: Ophthalmology. 2000 Apr;107(4):631-9
references.pmid: 10768324
references.citation: Curr Eye Res. 2010 Feb;35(2):176-83
references.pmid: 20136428