TRAIL death receptor-4, decoy receptor-1 and decoy receptor-2 expression on CD8+ T cells correlate with the disease severity in patients with rheumatoid arthritis.
BACKGROUND
Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disorder. Although the pathogenesis of disease is unclear, it is well known that T cells play a major role in both development and perpetuation of RA through activating macrophages and B cells. Since the lack of TNF-Related Apoptosis Inducing Ligand (TRAIL) expression resulted in defective thymocyte apoptosis leading to an autoimmune disease, we explored evidence for alterations in TRAIL/TRAIL receptor expression on peripheral T lymphocytes in the molecular mechanism of RA development.


METHODS
The expression of TRAIL/TRAIL receptors on T cells in 20 RA patients and 12 control individuals were analyzed using flow cytometry. The correlation of TRAIL and its receptor expression profile was compared with clinical RA parameters (RA activity scored as per DAS28) using Spearman Rho Analysis.


RESULTS
While no change was detected in the ratio of CD4+ to CD8+ T cells between controls and RA patient groups, upregulation of TRAIL and its receptors (both death and decoy) was detected on both CD4+ and CD8+ T cells in RA patients compared to control individuals. Death Receptor-4 (DR4) and the decoy receptors DcR1 and DcR2 on CD8+ T cells, but not on CD4+ T cells, were positively correlated with patients' DAS scores.


CONCLUSIONS
Our data suggest that TRAIL/TRAIL receptor expression profiles on T cells might be important in revelation of RA pathogenesis.
Bisgin
Atil
A
Department of Medical Genetics, Human Gene and Cell Therapy Center of Akdeniz University Hospitals and Clinics, Antalya, Turkey.
Terzioglu
Ender
E
Aydin
Cigdem
C
Yoldas
Burcak
B
Yazisiz
Veli
V
Balci
Nilufer
N
Bagci
Huseyin
H
Gorczynski
Reginald M
RM
Akdis
Cezmi A
CA
Sanlioglu
Salih
S
D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins / Q000096:biosynthesis; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis*; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D053319:Tumor Necrosis Factor Decoy Receptors / Q000096:biosynthesis*
D058851:GPI-Linked Proteins; D018124:Receptors, Tumor Necrosis Factor; D053320:Receptors, Tumor Necrosis Factor, Member 10c; C108661:TNFRSF10C protein, human; C451501:TNFRSF10D protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; C509611:decoy receptor 2, rat
J Clin Invest. 2003 Nov;112(9):1332-41
14597760
J Leukoc Biol. 2005 Sep;78(3):575-84
15894586
Scand J Rheumatol. 1999;28(3):166-70
10380839
Rheumatology (Oxford). 2007 May;46(5):783-9
17309888
J Urol. 2007 Jan;177(1):359-64
17162091
Arthritis Rheum. 1998 Jun;41(6):951-62
9627005
Pancreas. 2009 Mar;38(2):154-60
18981952
Cell. 1995 Jun 16;81(6):935-46
7540117
Cell Immunol. 2004 Sep-Oct;231(1-2):1-7
15919363
Adv Immunol. 1998;68:315-32
9505093
Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):716-23
17512128
J Clin Invest. 2003 Nov;112(9):1315-7
14597758
J Rheumatol Suppl. 2007 Jul;79:15-20
17611974
Hum Gene Ther. 2009 Oct;20(10):1177-89
19572802
Cancer Gene Ther. 2006 Jan 1;13(1):21-31
16052230
Pancreas. 2008 May;36(4):385-93
18437085
Arthritis Rheum. 2004 Sep;50(9):2775-85
15457445
Mol Ther. 2002 May;5(5 Pt 1):547-54
11991745
Curr Opin Rheumatol. 1997 May;9(3):236-40
9204259
Cell Death Differ. 2000 Jul;7(7):637-44
10889508
Curr Opin Immunol. 1998 Oct;10(5):559-63
9794836
Curr Opin Immunol. 1994 Dec;6(6):913-20
7536012
Cell Immunol. 2005 Jun;235(2):117-21
16226734
Hum Gene Ther. 2007 Jan;18(1):39-50
17187448
Nephrol Dial Transplant. 2002 May;17(5):697-700
11981048
Nat Clin Pract Rheumatol. 2006 Apr;2(4):201-10
16932686
Med Clin North Am. 1997 Jan;81(1):29-55
9012754
J Exp Med. 2004 Aug 2;200(3):277-85
15280421
Gene Ther. 2003 Jun;10(12):1055-60
12776164
Cancer Gene Ther. 2007 Dec;14(12):976-84
17853923
J Immunol. 1999 Mar 1;162(5):2597-605
10072501
J Exp Med. 2000 Apr 3;191(7):1095-104
10748228
Urol Oncol. 2008 Mar-Apr;26(2):158-65
18312935
N Engl J Med. 1996 Nov 28;335(22):1643-9
8929361
Immunol Cell Biol. 2001 Oct;79(5):502-6
11564158
FEBS Lett. 2005 Nov 21;579(28):6465-72
16289096
Cell Immunol. 2008 May-Jun;253(1-2):92-101
18649874
J Virol. 2001 Nov;75(22):11128-36
11602752
Nat Immunol. 2003 Mar;4(3):255-60
12577054
J Immunol. 2001 Aug 1;167(3):1245-53
11466340
Eur J Immunol. 2003 Jan;33(1):215-23
12594850
Rheumatology (Oxford). 1999 Feb;38(2):103-12
10342621
Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9203-8
10922071
Clin Rheumatol. 2000;19(4):270-4
10941806