title: Skin-resident T cells: the ups and downs of on site immunity.
abstract: The cutaneous surface of a normal adult individual contains approximately 20 billion T cells, nearly twice the number present in the entire circulation. Recent studies have shown a role for these cells in both normal immunity and in inflammatory skin diseases such as psoriasis. Regulatory T cells protect against autoimmune reactions to self antigens and assist in the resolution of cutaneous inflammation. However, they can also shield tumors from immune detection, allow latent infections to persist and can dysfunction under the conditions present in inflammatory skin diseases. Th17 T cells protect organisms against extracellular pathogens but also have a key role in the pathogenesis of psoriasis. Evidence suggests that effector memory T cells produced during immune reactions survive and persist long term within the skin, providing local and rapid protection against pathogen reexposure. This review summarizes the current understanding of how skin-resident T cells contribute to normal and aberrant immunity in the skin.
authors.affiliation: Department of Dermatology, Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. rclark1@partners.org
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Clark
mesh_terms: D000818:Animals; D015551:Autoimmunity; D004705:Endocytosis; D006801:Humans; D007107:Immune System; D007156:Immunologic Memory; D007249:Inflammation; D020381:Interleukin-17 / Q000737:chemistry; D051379:Mice; D008954:Models, Biological; D011565:Psoriasis / Q000276:immunology; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D012879:Skin Physiological Phenomena; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D020381:Interleukin-17
references.citation: Br J Dermatol. 2002 May;146(5):824-31
references.pmid: 12000379
references.citation: J Immunol. 1999 Feb 1;162(3):1246-51
references.pmid: 9973376
references.citation: Blood. 2005 Nov 1;106(9):3300-7
references.pmid: 16002422
references.citation: Arch Dermatol. 2003 Jul;139(7):857-66
references.pmid: 12873880
references.citation: Science. 2001 Mar 23;291(5512):2413-7
references.pmid: 11264538
references.citation: Nat Immunol. 2009 May;10(5):524-30
references.pmid: 19305395
references.citation: N Engl J Med. 2007 Feb 8;356(6):580-92
references.pmid: 17287478
references.citation: Nat Genet. 2009 Feb;41(2):199-204
references.pmid: 19169254
references.citation: J Immunol. 2004 Feb 1;172(3):1575-81
references.pmid: 14734737
references.citation: Mult Scler. 1999 Apr;5(2):101-4
references.pmid: 10335518
references.citation: J Exp Med. 2001 Apr 16;193(8):981-6
references.pmid: 11304559
references.citation: Nat Immunol. 2003 Apr;4(4):337-42
references.pmid: 12612581
references.citation: Annu Rev Immunol. 2004;22:217-46
references.pmid: 15032579
references.citation: J Immunol. 2004 May 15;172(10):6265-71
references.pmid: 15128815
references.citation: Immunol Lett. 2006 Nov 15;107(2):93-101
references.pmid: 16979761
references.citation: Nat Med. 2002 May;8(5):500-8
references.pmid: 11984595
references.citation: J Exp Med. 2006 Nov 27;203(12):2577-87
references.pmid: 17074928
references.citation: Nat Immunol. 2005 Nov;6(11):1133-41
references.pmid: 16200068
references.citation: Nat Immunol. 2007 Sep;8(9):950-7
references.pmid: 17676044
references.citation: J Exp Med. 2005 Jul 4;202(1):135-43
references.pmid: 15998792
references.citation: J Clin Invest. 2008 Nov;118(11):3639-50
references.pmid: 18924611
references.citation: Nature. 1999 Oct 14;401(6754):708-12
references.pmid: 10537110
references.citation: J Exp Med. 2008 Sep 29;205(10):2221-34
references.pmid: 18794336
references.citation: J Invest Dermatol. 2007 Oct;127(10):2391-8
references.pmid: 17508019
references.citation: Nat Rev Immunol. 2004 Apr;4(4):290-300
references.pmid: 15057787
references.citation: Blood. 2007 Jan 1;109(1):194-202
references.pmid: 16968902
references.citation: Science. 2008 Jan 11;319(5860):198-202
references.pmid: 18187654
references.citation: Nat Immunol. 2005 Apr;6(4):345-52
references.pmid: 15785760
references.citation: Br J Dermatol. 2007 Sep;157(3):531-9
references.pmid: 17596146
references.citation: Cancer Res. 2006 Jul 15;66(14):7301-9
references.pmid: 16849580
references.citation: J Invest Dermatol. 1987 May;88(5):569-73
references.pmid: 3494791
references.citation: J Invest Dermatol. 2008 May;128(5):1207-11
references.pmid: 18200064
references.citation: J Exp Med. 2004 Mar 1;199(5):731-6
references.pmid: 14981113
references.citation: J Exp Med. 2005 Sep 19;202(6):761-9
references.pmid: 16157683
references.citation: J Immunol. 2002 Dec 1;169(11):6210-7
references.pmid: 12444126
references.citation: J Immunol. 2008 Mar 1;180(5):3049-56
references.pmid: 18292527
references.citation: J Immunol. 2001 Jan 15;166(2):877-84
references.pmid: 11145663
references.citation: Nat Med. 2007 Apr;13(4):423-31
references.pmid: 17384649
references.citation: J Invest Dermatol. 2006 May;126(5):1059-70
references.pmid: 16484986
references.citation: Curr Top Microbiol Immunol. 1995;202:247-59
references.pmid: 7587366
references.citation: J Exp Med. 2002 Jan 7;195(1):135-41
references.pmid: 11781372
references.citation: Am J Pathol. 1994 Sep;145(3):550-60
references.pmid: 7915886
references.citation: J Immunol. 2008 Sep 15;181(6):3745-9
references.pmid: 18768825
references.citation: Proc Natl Acad Sci U S A. 1989 Aug;86(16):6367-71
references.pmid: 2474833
references.citation: J Immunol. 1994 Feb 15;152(4):1653-61
references.pmid: 8120375
references.citation: J Immunol. 2007 Feb 15;178(4):2229-40
references.pmid: 17277128
references.citation: J Immunol. 2006 Jan 15;176(2):1098-106
references.pmid: 16393998
references.citation: Hum Genet. 2007 Sep;122(2):201-6
references.pmid: 17587057
references.citation: J Clin Invest. 1999 May;103(9):1345-52
references.pmid: 10225978
references.citation: Arch Dermatol. 2008 Feb;144(2):200-7
references.pmid: 18283176
references.citation: J Immunol. 2006 Apr 1;176(7):4431-9
references.pmid: 16547281
references.citation: Nature. 1999 Aug 19;400(6746):776-80
references.pmid: 10466728
references.citation: J Exp Med. 2004 May 3;199(9):1265-75
references.pmid: 15123746
references.citation: Arthritis Rheum. 1999 May;42(5):963-70
references.pmid: 10323452
references.citation: J Immunol. 2001 Feb 1;166(3):1813-22
references.pmid: 11160228
references.citation: Am J Hum Genet. 2007 Feb;80(2):273-90
references.pmid: 17236132
references.citation: J Invest Dermatol. 2009 Jan;129(1):79-88
references.pmid: 18633443
references.citation: J Exp Med. 2007 Mar 19;204(3):595-603
references.pmid: 17325200
references.citation: J Virol. 2005 Dec;79(23):14843-51
references.pmid: 16282484
references.citation: J Allergy Clin Immunol. 2003 Sep;112(3):609-15
references.pmid: 13679823
references.citation: Nat Med. 2002 Feb;8(2):157-65
references.pmid: 11821900
references.citation: J Virol. 2005 Jun;79(12):7845-51
references.pmid: 15919938
references.citation: Nature. 2003 Jul 3;424(6944):88-93
references.pmid: 12840763
references.citation: J Immunol. 2008 Nov 1;181(9):5837-41
references.pmid: 18941171
references.citation: Immunity. 2006 Sep;25(3):511-20
references.pmid: 16973385
references.citation: Blood. 2008 Dec 15;112(13):4953-60
references.pmid: 18820132
references.citation: Curr Opin Immunol. 2005 Jun;17(3):326-32
references.pmid: 15886125
references.citation: J Immunol. 2006 Feb 1;176(3):1908-15
references.pmid: 16424222
references.citation: J Immunol. 2008 Oct 1;181(7):4733-41
references.pmid: 18802076
references.citation: Nature. 2001 Mar 1;410(6824):101-5
references.pmid: 11242050
references.citation: Curr Drug Targets Inflamm Allergy. 2004 Jun;3(2):157-61
references.pmid: 15180468
references.citation: J Invest Dermatol. 1997 Sep;109(3):271-5
references.pmid: 9284089
references.citation: J Immunol. 1998 Nov 1;161(9):4902-8
references.pmid: 9794424
references.citation: J Exp Med. 1990 Mar 1;171(3):801-17
references.pmid: 2307933
references.citation: Semin Cancer Biol. 2006 Apr;16(2):98-105
references.pmid: 16378733
references.citation: Nature. 2007 Feb 8;445(7128):648-51
references.pmid: 17187052
references.citation: Nature. 2002 Dec 5;420(6915):502-7
references.pmid: 12466842
references.citation: Cell. 1996 Aug 23;86(4):643-53
references.pmid: 8752218
references.citation: J Immunol. 2003 Jan 1;170(1):394-9
references.pmid: 12496424
references.citation: J Immunol. 2005 Jan 1;174(1):164-73
references.pmid: 15611238
references.citation: J Infect Dis. 2004 Aug 1;190(3):624-31
references.pmid: 15243941
references.citation: Immunity. 2008 Apr;28(4):454-67
references.pmid: 18400188
references.citation: Am J Pathol. 1995 Jul;147(1):79-91
references.pmid: 7604887
references.citation: J Exp Med. 2006 Oct 30;203(11):2451-60
references.pmid: 17015634
references.citation: J Invest Dermatol. 2008 Jul;128(7):1653-61
references.pmid: 18219280
references.citation: J Exp Med. 1998 Jan 19;187(2):205-16
references.pmid: 9432978
references.citation: Annu Rev Immunol. 2004;22:745-63
references.pmid: 15032595
references.citation: J Exp Med. 2005 Jan 17;201(2):303-16
references.pmid: 15642741
references.citation: Science. 2006 Dec 1;314(5804):1461-3
references.pmid: 17068223
references.citation: J Exp Med. 1991 Dec 1;174(6):1461-6
references.pmid: 1720810
references.citation: J Exp Med. 2004 Jan 5;199(1):125-30
references.pmid: 14707118
references.citation: J Exp Med. 2001 May 7;193(9):1105-12
references.pmid: 11342595
references.citation: Arch Dermatol Res. 1989;281(1):24-30
references.pmid: 2525009
references.citation: Nat Rev Immunol. 2004 Mar;4(3):211-22
references.pmid: 15039758
references.citation: Nat Immunol. 2005 Nov;6(11):1123-32
references.pmid: 16200070