The yin and yang of regulatory T cells and inflammation in RA.
Rheumatoid arthritis (RA) is characterized by chronic inflammation leading to joint destruction. Regulatory T (T(REG)) cells are potent suppressors of autoimmunity, but are not capable of controlling every aspect of the inflammatory reaction. We have found that T(REG)-cell function is abnormal in patients with RA, and that a distinct population of T(REG) cells with potent suppressive properties is induced after therapy with inhibitors of tumor necrosis factor. In this Review, we discuss the mutual interactions between the opposing forces of T(REG) cells and inflammation in the context of RA. Therapeutic approaches that enhance T(REG)-cell function whilst controlling inflammation are likely to be the most effective strategies for restoring immune tolerance in patients with this disease.
Notley
Clare A
CA
Centre for Rheumatology Research, Windeyer Institute of Medical Science, University College London, London W1P 4JF, UK.
Ehrenstein
Michael R
MR
D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D015703:Antigens, CD / Q000378:metabolism; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018501:Antirheumatic Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha
Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17034-9
17942669
Nat Immunol. 2010 Jan;11(1):7-13
20016504
J Immunol. 2009 Dec 1;183(11):7602-10
19917691
Blood. 2009 Oct 29;114(18):3727-35
19641188
Arthritis Res. 2001;3(3):168-77
11299057
Nature. 2007 Feb 15;445(7129):771-5
17220874
J Exp Med. 2001 Jun 4;193(11):1303-10
11390437
Arthritis Rheum. 2010 Jan;62(1):171-8
20039431
J Exp Med. 2003 Dec 15;198(12):1875-86
14676299
Eur J Immunol. 2008 Jun;38(6):1621-30
18493981
Nature. 2006 May 11;441(7090):235-8
16648838
J Immunol. 2007 Jan 15;178(2):732-9
17202333
Int Immunol. 2007 Jun;19(6):785-99
17545278
Proc Natl Acad Sci U S A. 2009 Nov 10;106(45):19078-83
19884493
Lupus. 2009 Jun;18(7):586-96
19433458
J Exp Med. 2008 Sep 1;205(9):1993-2004
18725526
Nat Immunol. 2009 Sep;10(9):1000-7
19633673
Nat Immunol. 2003 Apr;4(4):337-42
12612581
J Immunol. 1997 Jun 1;158(11):5501-6
9164973
J Clin Invest. 2005 Jul;115(7):1923-33
15937545
Science. 2003 Feb 14;299(5609):1057-61
12522256
J Immunol. 2010 Apr 1;184(7):3336-40
20200272
J Exp Med. 2008 Oct 27;205(11):2491-7
18936235
J Exp Med. 2007 Jul 9;204(7):1543-51
17591856
Nat Med. 2007 Nov;13(11):1299-307
17922010
Nat Immunol. 2007 Sep;8(9):950-7
17676044
Immunity. 2008 Jul 18;29(1):44-56
18585065
J Exp Med. 2007 Jan 22;204(1):33-9
17200409
Arthritis Rheum. 2009 Apr;60(4):1065-75
19333922
J Immunol. 2004 May 15;172(10):6003-10
15128783
J Immunol. 2009 Jan 1;182(1):259-73
19109157
J Immunol. 2008 Apr 15;180(8):5393-401
18390721
Science. 2003 Feb 14;299(5609):1033-6
12532024
Immunity. 2009 Oct 16;31(4):609-20
19800266
Nat Med. 2007 Apr;13(4):423-31
17384649
Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6659-64
16617117
Nat Clin Pract Oncol. 2008 Dec;5(12):714-26
18839006
Joint Bone Spine. 2008 Jul;75(4):373-5
18571969
J Immunol. 2003 Mar 1;170(5):2655-62
12594294
Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):1903-8
19174509
J Immunol. 2007 Jul 1;179(1):154-61
17579033
J Immunol. 1998 Aug 1;161(3):1542-8
9686622
PLoS Biol. 2007 Feb;5(2):e38
17298177
J Exp Med. 2007 Aug 6;204(8):1849-61
17635957
Infect Immun. 2010 Jan;78(1):32-8
19901061
Science. 2008 Oct 10;322(5899):271-5
18845758
Arthritis Rheum. 2004 Sep;50(9):2775-85
15457445
Arthritis Rheum. 2010 Apr;62(4):929-39
20131262
Inflamm Res. 2002 Feb;51(2):102-4
11930902
Nat Rev Rheumatol. 2009 Oct;5(10):578-82
19798034
Immunol Cell Biol. 2009 Mar-Apr;87(3):195-202
19172156
Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12099-104
17623780
Mucosal Immunol. 2009 Sep;2(5):403-11
19587639
Arthritis Rheum. 2005 Sep;52(9):2686-92
16142748
Science. 2010 Apr 16;328(5976):372-6
20339032
J Exp Med. 2004 Aug 2;200(3):277-85
15280421
Blood. 2007 Oct 15;110(8):2983-90
17644734
Immunity. 2008 May;28(5):687-97
18468463
Blood. 2006 Jul 1;108(1):253-61
16537805
J Clin Invest. 2008 Oct;118(10):3411-9
18769633
Eur J Immunol. 2007 Oct;37(10):2744-52
17823984
J Exp Med. 2006 Jul 10;203(7):1701-11
16818678
J Immunol. 2003 Dec 1;171(11):6173-7
14634133
Eur J Immunol. 2009 Dec;39(12):3315-22
19750484
J Immunol. 2001 Aug 1;167(3):1245-53
11466340
Arthritis Rheum. 2007 Mar;56(3):732-42
17328044
Blood. 2009 Apr 30;113(18):4240-9
19171879
Arthritis Res Ther. 2005;7(2):R291-301
15743476
Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6232-7
19325128
Proc Natl Acad Sci U S A. 2009 May 26;106(21):8635-40
19439651
Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19396-401
19036923