Skip to main content
Top
Published in: Journal of Clinical Immunology 1/2013

01-01-2013 | Original Research

Levels of Circulating Th17 Cells and Regulatory T Cells in Ankylosing Spondylitis Patients with an Inadequate Response to Anti−TNF-α Therapy

Authors: Li Xueyi, Chen Lina, Wu Zhenbiao, Han Qing, Li Qiang, Ping Zhu

Published in: Journal of Clinical Immunology | Issue 1/2013

Login to get access

Abstract

Purpose

To investigate the effects of TNF-α blockage on levels of circulating Th17, Treg and their related cytokines in ankylosing spondylitis (AS) patients with different response to anti-TNF-α therapy.

Methods

The frequencies of circulating Th17 and Treg and serum levels of related cytokines were determined using flow cytometry analysis and ELISA, respectively, in 222 AS patients both before (baseline) and 6 months after anti-TNF-α therapy. Therapeutic response was defined according to ASAS (Assessment in Spondyloarthritis International Society) response criteria.

Results

Significantly higher baseline circulating Th17 and serum TNF-α, IL-6, IL-17, IL-23 were observed in active AS patients than in healthy controls. After anti-TNF-α therapy, 168 patients (75.7 %) were responders and 54 (24.3 %) were non-responders. Frequencies of Th17 significantly decreased in responders, but significantly increased in non-responders. Treg increased significantly in responders but decreased significantly in non-responders. Levels of TNF-α, IL-6, IL-17, and IL-23 were significantly decreased in responders. In contrast, IL-17 and IL-23 significantly increased in non-responders. TGF-β were significantly increased only in responders, whereas no significant changes were seen in IL-10 in either responders or non-responders. Spearman correlation analysis showed that frequencies of Th17 and levels of TNF-α, IL-6, IL-17, and IL-23 were positively correlated with BASDAI score. They were also positively correlated with BASFI score except for IL-6. Treg were found to be negatively correlated with BASDAI score.

Conclusions

The beneficial effect of anti-TNF-α therapy in AS might not only neutralize the effects of TNF-α but also down-regulate Th17 and Th17-related cytokines accompanied by up-regulating the Treg/TGF-β axis in responders.
Literature
1.
go back to reference Baek HJ, Shin KC, et al. Clinical features of adult-onset ankylosing spondylitis in Korean patients: patients with peripheral joint disease (PJD) have less severe spinal disease course than those without PJD. Rheumatology (Oxford). 2004;43(12):1526–31.CrossRef Baek HJ, Shin KC, et al. Clinical features of adult-onset ankylosing spondylitis in Korean patients: patients with peripheral joint disease (PJD) have less severe spinal disease course than those without PJD. Rheumatology (Oxford). 2004;43(12):1526–31.CrossRef
3.
go back to reference Szalay B, Mészáros G, Cseh Á, Ács L, Deák M, Kovács L, Vásárhelyi B, Balog A. Adaptive immunity in ankylosing spondylitis: phenotype and functional alterations of T-cells before and during infliximab therapy. Clin Dev Immunol. 2012;2012:808724. Epub 2011 Sep 28. Szalay B, Mészáros G, Cseh Á, Ács L, Deák M, Kovács L, Vásárhelyi B, Balog A. Adaptive immunity in ankylosing spondylitis: phenotype and functional alterations of T-cells before and during infliximab therapy. Clin Dev Immunol. 2012;2012:808724. Epub 2011 Sep 28.
4.
go back to reference Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, et al. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Genet. 2007;39(11):1329–37.PubMedCrossRef Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, et al. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Genet. 2007;39(11):1329–37.PubMedCrossRef
5.
go back to reference Rueda B, Orozco G, Raya E, Fernandez-Sueiro JL, Mulero J, Blanco FJ, et al. The IL23R Arg381Gln non-synonymous polymorphism confers susceptibility to ankylosing spondylitis. Ann Rheum Dis. 2008;67(10):1451–4.PubMedCrossRef Rueda B, Orozco G, Raya E, Fernandez-Sueiro JL, Mulero J, Blanco FJ, et al. The IL23R Arg381Gln non-synonymous polymorphism confers susceptibility to ankylosing spondylitis. Ann Rheum Dis. 2008;67(10):1451–4.PubMedCrossRef
6.
go back to reference Karaderi T, Harvey D, Farrar C, Appleton LH, Stone MA, Sturrock RD, et al. Association between the interleukin 23 receptor and ankylosing spondylitis is confirmed by a new UK case–control study and meta-analysis of published series. Rheumatology (Oxford). 2009;48(4):386–9.CrossRef Karaderi T, Harvey D, Farrar C, Appleton LH, Stone MA, Sturrock RD, et al. Association between the interleukin 23 receptor and ankylosing spondylitis is confirmed by a new UK case–control study and meta-analysis of published series. Rheumatology (Oxford). 2009;48(4):386–9.CrossRef
7.
go back to reference Rahman P, Inman RD, Gladman DD, Reeve JP, Peddle L, Maksymowych WP. Association of interleukin-23 receptor variants with ankylosing spondylitis. Arthritis Rheum. 2008;58(4):1020–5.PubMedCrossRef Rahman P, Inman RD, Gladman DD, Reeve JP, Peddle L, Maksymowych WP. Association of interleukin-23 receptor variants with ankylosing spondylitis. Arthritis Rheum. 2008;58(4):1020–5.PubMedCrossRef
8.
go back to reference Shen H, Goodall JC, Hill Gaston JS. Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis Rheum. 2009;60(6):1647–56.PubMedCrossRef Shen H, Goodall JC, Hill Gaston JS. Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis Rheum. 2009;60(6):1647–56.PubMedCrossRef
9.
go back to reference Jandus C, Bioley G, Rivals JP, Dudler J, Speiser D, Romero P. Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides. Arthritis Rheum. 2008;58(8):2307–17.PubMedCrossRef Jandus C, Bioley G, Rivals JP, Dudler J, Speiser D, Romero P. Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides. Arthritis Rheum. 2008;58(8):2307–17.PubMedCrossRef
10.
go back to reference Bettelli E, Carrier Y, Gao W, Korn T, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006;441(7090):235–8.PubMedCrossRef Bettelli E, Carrier Y, Gao W, Korn T, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006;441(7090):235–8.PubMedCrossRef
11.
go back to reference Wu Y, Ren M, Yang R, et al. Reduced immunomodulation potential of bone marrow-derived mesenchymal stem cells induced CCR4 + CCR6 + Th/Treg cell subset imbalance in ankylosing spondylitis. Arthritis Res Ther. 2011;13(1): article R29. Wu Y, Ren M, Yang R, et al. Reduced immunomodulation potential of bone marrow-derived mesenchymal stem cells induced CCR4 + CCR6 + Th/Treg cell subset imbalance in ankylosing spondylitis. Arthritis Res Ther. 2011;13(1): article R29.
12.
go back to reference Bettelli E, Oukka M, Kuchroo VK. Th-17 cells in the circle of immunity and autoimmunity. Nat Immunol. 2007;8(4):345–50.PubMedCrossRef Bettelli E, Oukka M, Kuchroo VK. Th-17 cells in the circle of immunity and autoimmunity. Nat Immunol. 2007;8(4):345–50.PubMedCrossRef
13.
go back to reference Agarwal S, Misra R, Aggarwal A. Interleukin 17 levels are increased in juvenile idiopathic arthritis synovial fluid and induce synovial fibroblasts to produce proinflammatory cytokines and matrix metalloproteinases. J Rheumatol. 2008;35(3):515–9.PubMed Agarwal S, Misra R, Aggarwal A. Interleukin 17 levels are increased in juvenile idiopathic arthritis synovial fluid and induce synovial fibroblasts to produce proinflammatory cytokines and matrix metalloproteinases. J Rheumatol. 2008;35(3):515–9.PubMed
14.
go back to reference Van Bezooijen RL, Van Der Wee-Pals L, Papapoulos SE, Lowik CW. Interleukin 17 synergies with tumor necrosis factor alpha to induce cartilage destruction in vitro. Ann Rheum Dis. 2002;61(10):870–6.PubMedCrossRef Van Bezooijen RL, Van Der Wee-Pals L, Papapoulos SE, Lowik CW. Interleukin 17 synergies with tumor necrosis factor alpha to induce cartilage destruction in vitro. Ann Rheum Dis. 2002;61(10):870–6.PubMedCrossRef
15.
go back to reference Kikly K, Liu L, Na S, Sedgwick JD. The IL-23/Th(17) axis: therapeutic targets for autoimmune inflammation. Curr Opin Immunol. 2006;18(6):670–5.PubMedCrossRef Kikly K, Liu L, Na S, Sedgwick JD. The IL-23/Th(17) axis: therapeutic targets for autoimmune inflammation. Curr Opin Immunol. 2006;18(6):670–5.PubMedCrossRef
16.
go back to reference Cooper AM, Khader SA. IL-12p40: an inherently agonistic cytokine. Trends Immunol. 2007;28(1):33–8.PubMedCrossRef Cooper AM, Khader SA. IL-12p40: an inherently agonistic cytokine. Trends Immunol. 2007;28(1):33–8.PubMedCrossRef
17.
go back to reference Taylan A, Sari I, Kozaci DL, et al. Evaluation of the T helper 17 axis in ankylosing spondylitis. Rheumatol Int. 2011 Jul 16. [Epub ahead of print]. Taylan A, Sari I, Kozaci DL, et al. Evaluation of the T helper 17 axis in ankylosing spondylitis. Rheumatol Int. 2011 Jul 16. [Epub ahead of print].
18.
go back to reference Iwamoto S, Iwai S, Tsujiyama K, Kurahashi C, Takeshita K, Naoe M, Masunaga A, Ogawa Y, Oguchi K, Miyazaki A. TNF-alpha drives human CD14+ monocytes to differentiate into CD70+ dendritic cells evolving Th1 and Th17 responses. J Immunol. 2007;179(3):1449–57.PubMed Iwamoto S, Iwai S, Tsujiyama K, Kurahashi C, Takeshita K, Naoe M, Masunaga A, Ogawa Y, Oguchi K, Miyazaki A. TNF-alpha drives human CD14+ monocytes to differentiate into CD70+ dendritic cells evolving Th1 and Th17 responses. J Immunol. 2007;179(3):1449–57.PubMed
19.
go back to reference Ma HL, Napierata L, Stedman N, Benoit S, Collins M, Nickerson-Nutter C, Young DA. Tumor necrosis factor α blockade exacerbates murine psoriasis-like disease by enhancing Th17 function and decreasing expansion of Treg cells. Arthritis Rheum. 2010;62(2):430–40.PubMedCrossRef Ma HL, Napierata L, Stedman N, Benoit S, Collins M, Nickerson-Nutter C, Young DA. Tumor necrosis factor α blockade exacerbates murine psoriasis-like disease by enhancing Th17 function and decreasing expansion of Treg cells. Arthritis Rheum. 2010;62(2):430–40.PubMedCrossRef
20.
go back to reference Notley CA, Inglis JJ, Alzabin S, McCann FE, McNamee KE, Williams RO. Blockade of tumor necrosis factor in collagen-induced arthritis reveals a novel immunoregulatory pathway for Th1 and Th17 cells. J Exp Med. 2008;205(11):2491–7.PubMedCrossRef Notley CA, Inglis JJ, Alzabin S, McCann FE, McNamee KE, Williams RO. Blockade of tumor necrosis factor in collagen-induced arthritis reveals a novel immunoregulatory pathway for Th1 and Th17 cells. J Exp Med. 2008;205(11):2491–7.PubMedCrossRef
21.
go back to reference Carmona L, Gomez-Reino JJ. Survival of TNF antagonists in spondylarthritis is better than in rheumatoid arthritis. Arthritis Res Ther. 2006;8:R72.PubMedCrossRef Carmona L, Gomez-Reino JJ. Survival of TNF antagonists in spondylarthritis is better than in rheumatoid arthritis. Arthritis Res Ther. 2006;8:R72.PubMedCrossRef
22.
go back to reference McLeod C, Bagust A, Boland A, Dagenais P, Dickson R, Dundar Y, Hill RA, Jones A, Mujica Mota R, Walley T. Adalimumab, etanercept and infliximab for the treatment of ankylosing spondylitis: a systematic review and economic evaluation. Health Technol Assess. 2007;11(28):1–158. McLeod C, Bagust A, Boland A, Dagenais P, Dickson R, Dundar Y, Hill RA, Jones A, Mujica Mota R, Walley T. Adalimumab, etanercept and infliximab for the treatment of ankylosing spondylitis: a systematic review and economic evaluation. Health Technol Assess. 2007;11(28):1–158.
23.
go back to reference Gottlieb AB, Chamian F, Masud S, Cardinale I, Abello MV, Lowes MA, Chen F, Magliocco M, Krueger JG. TNF inhibition rapidly down-regulates multiple proinflammatory pathways in psoriasis plaques. J Immunol. 2005;175(4):2721–9.PubMed Gottlieb AB, Chamian F, Masud S, Cardinale I, Abello MV, Lowes MA, Chen F, Magliocco M, Krueger JG. TNF inhibition rapidly down-regulates multiple proinflammatory pathways in psoriasis plaques. J Immunol. 2005;175(4):2721–9.PubMed
24.
go back to reference Lina C, Conghua W, Nan L, Ping Z. Combined treatment of etanercept and MTX reverses Th1/Th2, Th17/Treg imbalance in patients with rheumatoid arthritis. J Clin Immunol. 2011;31(4):596–605.PubMedCrossRef Lina C, Conghua W, Nan L, Ping Z. Combined treatment of etanercept and MTX reverses Th1/Th2, Th17/Treg imbalance in patients with rheumatoid arthritis. J Clin Immunol. 2011;31(4):596–605.PubMedCrossRef
25.
go back to reference Yue C, You X, Zhao L, Wang H, Tang F, Zhang F, Zhang X, He W. The effects of adalimumab and methotrexate treatment on peripheral Th17 cells and IL-17/IL-6 secretion in the rheumatoid arthritis patients. Rheumatol Int. 2009;30(12):1553–7.PubMedCrossRef Yue C, You X, Zhao L, Wang H, Tang F, Zhang F, Zhang X, He W. The effects of adalimumab and methotrexate treatment on peripheral Th17 cells and IL-17/IL-6 secretion in the rheumatoid arthritis patients. Rheumatol Int. 2009;30(12):1553–7.PubMedCrossRef
26.
go back to reference Van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984;27(4):361–8.PubMedCrossRef Van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984;27(4):361–8.PubMedCrossRef
27.
go back to reference Zochling J, van der Heijde D, Dougados M, et al. Current evidence for the management of ankylosing spondylitis: a systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis. Ann Rheum Dis. 2006;65(4):423–32.PubMedCrossRef Zochling J, van der Heijde D, Dougados M, et al. Current evidence for the management of ankylosing spondylitis: a systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis. Ann Rheum Dis. 2006;65(4):423–32.PubMedCrossRef
28.
go back to reference Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease status in ankylosing spondylitis: the bath ankylosing spondylitis disease activity index. J Rheumatol. 1994;21(12):2286–91.PubMed Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease status in ankylosing spondylitis: the bath ankylosing spondylitis disease activity index. J Rheumatol. 1994;21(12):2286–91.PubMed
29.
go back to reference Calin A, Garrett S, Whitelock H, Kennedy LG, O’Hea J, Mallorie P, et al. A new approach to defining functional ability in ankylosing spondylitis: the development of the bath ankylosing spondylitis functional index. J Rheumatol. 1994;21(12):2281–5.PubMed Calin A, Garrett S, Whitelock H, Kennedy LG, O’Hea J, Mallorie P, et al. A new approach to defining functional ability in ankylosing spondylitis: the development of the bath ankylosing spondylitis functional index. J Rheumatol. 1994;21(12):2281–5.PubMed
30.
go back to reference Sieper J, Braun J, Rudwaleit M, Boonen A, Zink A. Ankylosing spondylitis: an overview. Ann Rheum Dis. 2002;61(3):iii8–18.PubMed Sieper J, Braun J, Rudwaleit M, Boonen A, Zink A. Ankylosing spondylitis: an overview. Ann Rheum Dis. 2002;61(3):iii8–18.PubMed
32.
go back to reference Shahrara S, Huang Q, Mandelin 2nd AM, Pope RM. TH-17 cells in rheumatoid arthritis. Arthritis Res Ther. 2008;10(4):R93.PubMedCrossRef Shahrara S, Huang Q, Mandelin 2nd AM, Pope RM. TH-17 cells in rheumatoid arthritis. Arthritis Res Ther. 2008;10(4):R93.PubMedCrossRef
33.
go back to reference Fitch E, Harper E, Skorcheva I, Kurtz SE, Blauvelt A. Pathophysiology of psoriasis: recent advances on IL-23 and Th17 cytokines. Curr Rheumatol Rep. 2007;9(6):461–7.PubMedCrossRef Fitch E, Harper E, Skorcheva I, Kurtz SE, Blauvelt A. Pathophysiology of psoriasis: recent advances on IL-23 and Th17 cytokines. Curr Rheumatol Rep. 2007;9(6):461–7.PubMedCrossRef
34.
go back to reference Maloy KJ. The Interleukin-23/Interleukin-17 axis in intestinal inflammation. J Intern Med. 2008;263(6):584–90.PubMedCrossRef Maloy KJ. The Interleukin-23/Interleukin-17 axis in intestinal inflammation. J Intern Med. 2008;263(6):584–90.PubMedCrossRef
35.
go back to reference Wendling D, Cedoz JP, Racadot E, Dumoulin G. Serum IL-17, BMP-7, and bone turnover markers in patients with ankylosing spondylitis. Joint Bone Spine. 2007;74(3):304–5.PubMedCrossRef Wendling D, Cedoz JP, Racadot E, Dumoulin G. Serum IL-17, BMP-7, and bone turnover markers in patients with ankylosing spondylitis. Joint Bone Spine. 2007;74(3):304–5.PubMedCrossRef
36.
go back to reference Wang X, Lin Z, Wei Q, Jiang Y, Gu J. Expression of IL-23 and IL-17 and effect of IL-23 on IL-17 production in ankylosing spondylitis. Rheumatol Int. 2009;29(11):1343–7.PubMedCrossRef Wang X, Lin Z, Wei Q, Jiang Y, Gu J. Expression of IL-23 and IL-17 and effect of IL-23 on IL-17 production in ankylosing spondylitis. Rheumatol Int. 2009;29(11):1343–7.PubMedCrossRef
37.
go back to reference Melis L, Vandooren B, Kruithof E, Jacques P, De Vos M, Mielants H, et al. Systemic levels of IL-23 are strongly associated with disease activity in rheumatoid arthritis but not spondyloarthritis. Ann Rheum Dis. 2010;69(3):618–23.PubMedCrossRef Melis L, Vandooren B, Kruithof E, Jacques P, De Vos M, Mielants H, et al. Systemic levels of IL-23 are strongly associated with disease activity in rheumatoid arthritis but not spondyloarthritis. Ann Rheum Dis. 2010;69(3):618–23.PubMedCrossRef
38.
go back to reference Nomura T, Abe Y, Kamada H, Shibata H, Kayamuro H, Inoue M, Kawara T, Arita S, Furuya T, Yamashita T, Nagano K, Yoshikawa T, Yoshioka Y, Mukai Y, Nakagawa S, Taniai M, Ohta T, Serada S, Naka T, Tsunoda S, Tsutsumi Y. Therapeutic effect of PEGylated TNFR 1-selective antagonistic mutant TNF in experimental autoimmune encephalomyelitis mice. J Control Release. 2011;149(1):8–14.PubMedCrossRef Nomura T, Abe Y, Kamada H, Shibata H, Kayamuro H, Inoue M, Kawara T, Arita S, Furuya T, Yamashita T, Nagano K, Yoshikawa T, Yoshioka Y, Mukai Y, Nakagawa S, Taniai M, Ohta T, Serada S, Naka T, Tsunoda S, Tsutsumi Y. Therapeutic effect of PEGylated TNFR 1-selective antagonistic mutant TNF in experimental autoimmune encephalomyelitis mice. J Control Release. 2011;149(1):8–14.PubMedCrossRef
39.
go back to reference Raza K, Falciani F, Curnow SJ, Ross EJ, Lee CY, Akbar AN, Lord JM, Gordon C, Buckley CD, Salmon M. Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cells and stromal cell origin. Arthritis Res Ther. 2005;7(4):R784–95.PubMedCrossRef Raza K, Falciani F, Curnow SJ, Ross EJ, Lee CY, Akbar AN, Lord JM, Gordon C, Buckley CD, Salmon M. Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cells and stromal cell origin. Arthritis Res Ther. 2005;7(4):R784–95.PubMedCrossRef
40.
go back to reference Sato K, Suematsu A, Okamoto K, Yamaguchi A, Morishita Y, Kadono Y, Tanaka S, Kodama T, Akira S, Iwakura Y, Cua DJ, Takayanagi H. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med. 2006;203(12):2673–82.PubMedCrossRef Sato K, Suematsu A, Okamoto K, Yamaguchi A, Morishita Y, Kadono Y, Tanaka S, Kodama T, Akira S, Iwakura Y, Cua DJ, Takayanagi H. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med. 2006;203(12):2673–82.PubMedCrossRef
41.
go back to reference Jovanovic DV, Di Battista JA, Martel-Pelletier J, Jolicoeur FC, He Y, Zhang M, Mineau F, Pelletier JP. IL-17 stimulates the production of proinflammatory cytokines, IL-1β and TNF-α, by human macrophages. J Immunol. 1998;160(7):3513–21.PubMed Jovanovic DV, Di Battista JA, Martel-Pelletier J, Jolicoeur FC, He Y, Zhang M, Mineau F, Pelletier JP. IL-17 stimulates the production of proinflammatory cytokines, IL-1β and TNF-α, by human macrophages. J Immunol. 1998;160(7):3513–21.PubMed
42.
go back to reference Katz Y, Nadiv O, Beer Y. Interleukin-17 enhances tumor necrosis factor alpha-induced synthesis of interleukins1, 6, and 8 in skin and synovial fibroblasts: a possible role as a “fine-tuning cytokine” in inflammation processes. Arthritis Rheum. 2001;44(9):2176–84.PubMedCrossRef Katz Y, Nadiv O, Beer Y. Interleukin-17 enhances tumor necrosis factor alpha-induced synthesis of interleukins1, 6, and 8 in skin and synovial fibroblasts: a possible role as a “fine-tuning cytokine” in inflammation processes. Arthritis Rheum. 2001;44(9):2176–84.PubMedCrossRef
43.
go back to reference Langrish CL, Chen Y, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005;201(2):233–40.PubMedCrossRef Langrish CL, Chen Y, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005;201(2):233–40.PubMedCrossRef
44.
go back to reference Harrington LE, Hatton RD, et al. Interleukin 17-producing CD4 effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6(11):1123–32.PubMedCrossRef Harrington LE, Hatton RD, et al. Interleukin 17-producing CD4 effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6(11):1123–32.PubMedCrossRef
45.
go back to reference Zhou L, Ivanov II, Spolski R, Min R, Shenderov K, Egawa T, Levy DE, Leonard WJ, Littman DR. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol. 2007;8(9):967–74.PubMedCrossRef Zhou L, Ivanov II, Spolski R, Min R, Shenderov K, Egawa T, Levy DE, Leonard WJ, Littman DR. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol. 2007;8(9):967–74.PubMedCrossRef
47.
go back to reference Chen Z, Tato CM, Muul L, Laurence A, ÓShea JJ. Distinct regulation of interleukn-17 in human T helper lymphocytes. Arthritis Rheum. 2007;56(9):2936–46.PubMedCrossRef Chen Z, Tato CM, Muul L, Laurence A, ÓShea JJ. Distinct regulation of interleukn-17 in human T helper lymphocytes. Arthritis Rheum. 2007;56(9):2936–46.PubMedCrossRef
48.
go back to reference Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117(2):224–79.CrossRef Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117(2):224–79.CrossRef
49.
go back to reference Eissner G, Kolch W, Scheurich P. Ligands working as receptors: reverse signaling by members of the TNF superfamily enhances the plasticity of the immune system. Cytokine Growth Factor Rev. 2004;15(5):353–66.PubMedCrossRef Eissner G, Kolch W, Scheurich P. Ligands working as receptors: reverse signaling by members of the TNF superfamily enhances the plasticity of the immune system. Cytokine Growth Factor Rev. 2004;15(5):353–66.PubMedCrossRef
50.
go back to reference Mitoma H, Horiuchi T, Hatta N, Tsukamoto H, Harashima S, Kikuchi Y, et al. Infliximab induces potent anti-inflammatory responses by outside-to-inside signals through transmembrane TNF-alpha. Gastroenterology. 2005;128(2):376–92.PubMedCrossRef Mitoma H, Horiuchi T, Hatta N, Tsukamoto H, Harashima S, Kikuchi Y, et al. Infliximab induces potent anti-inflammatory responses by outside-to-inside signals through transmembrane TNF-alpha. Gastroenterology. 2005;128(2):376–92.PubMedCrossRef
51.
go back to reference Lundy SK, Sarkar S, Tesmer LA, Fox DA, Lundy SK, Sarkar S, Tesmer LA, Fox DA. Cells of the synovium in rheumatoid arthritis. T lymphocytes. Arthritis Res Ther. 2007;9(1):202–12.PubMedCrossRef Lundy SK, Sarkar S, Tesmer LA, Fox DA, Lundy SK, Sarkar S, Tesmer LA, Fox DA. Cells of the synovium in rheumatoid arthritis. T lymphocytes. Arthritis Res Ther. 2007;9(1):202–12.PubMedCrossRef
52.
go back to reference Zhang J, Wang X, Fahmi H, Wojcik S, Fikes J, Yu Y, Wu J, Luo H. Role of TL1A in the pathogenesis of rheumatoid arthritis. J Immunol. 2009;183(8):5350–7.PubMedCrossRef Zhang J, Wang X, Fahmi H, Wojcik S, Fikes J, Yu Y, Wu J, Luo H. Role of TL1A in the pathogenesis of rheumatoid arthritis. J Immunol. 2009;183(8):5350–7.PubMedCrossRef
53.
go back to reference Goldberg M, Nadiv O, Luknar-Gabor N, Agar G, Beer Y, Katz Y. Synergism between tumor necrosis factor alpha and interleukin-17 to induce IL-23 p19 expression in fibroblast-like synoviocytes. Mol Immunol. 2009;46(8–9):1854–9.PubMedCrossRef Goldberg M, Nadiv O, Luknar-Gabor N, Agar G, Beer Y, Katz Y. Synergism between tumor necrosis factor alpha and interleukin-17 to induce IL-23 p19 expression in fibroblast-like synoviocytes. Mol Immunol. 2009;46(8–9):1854–9.PubMedCrossRef
54.
go back to reference Ogawa K, Matsumoto T, Esaki M, Torisu T, Iida M. Profiles of circulating cytokines in patients with Crohn’s disease under maintenance therapy with infliximab. J Crohns Colitis. 2012;6(5):529–35.PubMedCrossRef Ogawa K, Matsumoto T, Esaki M, Torisu T, Iida M. Profiles of circulating cytokines in patients with Crohn’s disease under maintenance therapy with infliximab. J Crohns Colitis. 2012;6(5):529–35.PubMedCrossRef
55.
go back to reference Charles P, Elliott MJ, Davis D, Potter A, Kalden JR, Antoni C, et al. Regulation of cytokines, cytokine inhibitors, and acute-phase proteins following anti-TNF-α therapy in rheumatoid arthritis. J Immunol. 1999;163(3):1521–8.PubMed Charles P, Elliott MJ, Davis D, Potter A, Kalden JR, Antoni C, et al. Regulation of cytokines, cytokine inhibitors, and acute-phase proteins following anti-TNF-α therapy in rheumatoid arthritis. J Immunol. 1999;163(3):1521–8.PubMed
56.
go back to reference Ehrenstein MR, Evans JG, et al. Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy. J Exp Med. 2004;200(3):277–85.PubMedCrossRef Ehrenstein MR, Evans JG, et al. Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy. J Exp Med. 2004;200(3):277–85.PubMedCrossRef
Metadata
Title
Levels of Circulating Th17 Cells and Regulatory T Cells in Ankylosing Spondylitis Patients with an Inadequate Response to Anti−TNF-α Therapy
Authors
Li Xueyi
Chen Lina
Wu Zhenbiao
Han Qing
Li Qiang
Ping Zhu
Publication date
01-01-2013
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 1/2013
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-012-9774-0

Other articles of this Issue 1/2013

Journal of Clinical Immunology 1/2013 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.