Skip to main content
Erschienen in: Rheumatology International 9/2012

01.09.2012 | Original Article

Disturbed Th17/Treg balance in patients with rheumatoid arthritis

verfasst von: Qian Niu, Bei Cai, Zhuo-chun Huang, Yun-ying Shi, Lan-lan Wang

Erschienen in: Rheumatology International | Ausgabe 9/2012

Einloggen, um Zugang zu erhalten

Abstract

Proinflammatory Th17 cells and CD4+CD25+ regulatory T (Treg) cells are two newly identified T lymphocyte subsets, which have opposite effects on autoimmunity and inflammation. To assess the Th17/Treg pattern and cytokine microenvironment in peripheral blood of patients with RA, we included 66 RA patients and 20 healthy volunteers. Of all these subjects, peripheral Th17 and Treg frequencies were analyzed by flow cytometry (FCM) and the plasma levels of interleukin (IL)-17, 23, 6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1 were detected by ELISA. The results demonstrated that RA patients revealed an obvious increase in peripheral Th17 frequencies and levels of Th17-related cytokines (IL-17, IL-23, IL-6, TNF-α) while a significant decrease in Treg frequencies and Treg-related cytokine (TGF-β1) levels when compared with healthy people. Our study indicated that development of RA is associated with peripheral Th17/Treg imbalance and characterized by a proinflammatory cytokine microenvironment, which supports continuing generation of Th17 cells.
Literatur
2.
Zurück zum Zitat McInnes IB, Schett G (2007) Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 7:429–442PubMedCrossRef McInnes IB, Schett G (2007) Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 7:429–442PubMedCrossRef
3.
Zurück zum Zitat Falgarone G, Duclos M, Boissier MC (2007) TNF-α antagonists in rheumatoid arthritis patients seen in everyday practice. Joint Bone Spine 74:523–526PubMedCrossRef Falgarone G, Duclos M, Boissier MC (2007) TNF-α antagonists in rheumatoid arthritis patients seen in everyday practice. Joint Bone Spine 74:523–526PubMedCrossRef
4.
Zurück zum Zitat Bettelli E, Oukka M, Kuchroo VK (2007) T(H)-17 cells in the circle of immunity and autoimmunity. Nat Immunol 8:345–350PubMedCrossRef Bettelli E, Oukka M, Kuchroo VK (2007) T(H)-17 cells in the circle of immunity and autoimmunity. Nat Immunol 8:345–350PubMedCrossRef
5.
Zurück zum Zitat Marie-Christophe B, Eric A, Geraldine F et al (2008) Shifting the imbalance from Th1/Th2 to Th17/treg: The changing rheumatoid arthritis paradigm. Joint Bone Spine 75:373–375CrossRef Marie-Christophe B, Eric A, Geraldine F et al (2008) Shifting the imbalance from Th1/Th2 to Th17/treg: The changing rheumatoid arthritis paradigm. Joint Bone Spine 75:373–375CrossRef
6.
Zurück zum Zitat Arnett FC, Edworthy SM, Bloch DA et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324PubMedCrossRef Arnett FC, Edworthy SM, Bloch DA et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324PubMedCrossRef
7.
Zurück zum Zitat Prevoo ML, van’t Hof MA, Kuper HH et al (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38:44–48PubMedCrossRef Prevoo ML, van’t Hof MA, Kuper HH et al (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38:44–48PubMedCrossRef
8.
Zurück zum Zitat Manoury-Schwartz B, Chiocchia G, Bessis N et al (1997) High susceptibility to collagen-induced arthritis in mice lacking IFN-gamma receptors. J Immunol 158:5501–5506PubMed Manoury-Schwartz B, Chiocchia G, Bessis N et al (1997) High susceptibility to collagen-induced arthritis in mice lacking IFN-gamma receptors. J Immunol 158:5501–5506PubMed
9.
Zurück zum Zitat Boissier MC, Chiocchia G, Bessis N et al (1995) Biphasic effect of interferongamma in murine collagen-induced arthritis. Eur J Immunol 25:1184–1190PubMedCrossRef Boissier MC, Chiocchia G, Bessis N et al (1995) Biphasic effect of interferongamma in murine collagen-induced arthritis. Eur J Immunol 25:1184–1190PubMedCrossRef
10.
Zurück zum Zitat Eastaff-Leung N, Mabarrack N, Barbour A et al (2010) Foxp3+ regulatory T cells, Th17 effector cells, and cytokine environment in inflammatory bowel disease. J Clin Immunol 30:80–89PubMedCrossRef Eastaff-Leung N, Mabarrack N, Barbour A et al (2010) Foxp3+ regulatory T cells, Th17 effector cells, and cytokine environment in inflammatory bowel disease. J Clin Immunol 30:80–89PubMedCrossRef
11.
Zurück zum Zitat Nistala K, Moncrieffe H, Newton KR et al (2008) Interleukin-17—producing T cells are enriched in the joints of children with arthritis, but have a reciprocal relationship to regulatory T cell numbers. Arthritis Rheum 58:875–887PubMedCrossRef Nistala K, Moncrieffe H, Newton KR et al (2008) Interleukin-17—producing T cells are enriched in the joints of children with arthritis, but have a reciprocal relationship to regulatory T cell numbers. Arthritis Rheum 58:875–887PubMedCrossRef
12.
Zurück zum Zitat Chengl X, Yu X, Ding Y-J et al (2008) The Th17/Treg imbalance in patients with acute coronary syndrome. Clin Immunol 127:89–97CrossRef Chengl X, Yu X, Ding Y-J et al (2008) The Th17/Treg imbalance in patients with acute coronary syndrome. Clin Immunol 127:89–97CrossRef
13.
Zurück zum Zitat Paradowska A, Maśliński W, Grzybowska-Kowalczyk A et al (2007) The function of interleukin 17 in the pathogenesis of rheumatoid arthritis. Arch Immunol Ther Exp 55:329–334CrossRef Paradowska A, Maśliński W, Grzybowska-Kowalczyk A et al (2007) The function of interleukin 17 in the pathogenesis of rheumatoid arthritis. Arch Immunol Ther Exp 55:329–334CrossRef
14.
Zurück zum Zitat Kim KW, Cho ML, Park MK et al (2005) Increased interleukin-17 production via a phosphoinositide 3-kinase/Akt and nuclear factor κB-dependent pathway in patients with rheumatoid arthritis. Arthritis Res Ther 7:R139–R148PubMedCrossRef Kim KW, Cho ML, Park MK et al (2005) Increased interleukin-17 production via a phosphoinositide 3-kinase/Akt and nuclear factor κB-dependent pathway in patients with rheumatoid arthritis. Arthritis Res Ther 7:R139–R148PubMedCrossRef
15.
Zurück zum Zitat Berg WB, Miossec P (2009) IL-17 as a future therapeutic target for rheumatoid arthritis. Nat Rev Rheumatol 5:549–553PubMedCrossRef Berg WB, Miossec P (2009) IL-17 as a future therapeutic target for rheumatoid arthritis. Nat Rev Rheumatol 5:549–553PubMedCrossRef
16.
Zurück zum Zitat Lubberts E (2008) IL-17/Th17 targeting: on the road to prevent chronic destructive arthritis? Cytokine 41:84–91PubMedCrossRef Lubberts E (2008) IL-17/Th17 targeting: on the road to prevent chronic destructive arthritis? Cytokine 41:84–91PubMedCrossRef
17.
Zurück zum Zitat Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299:1057–1061PubMedCrossRef Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299:1057–1061PubMedCrossRef
18.
Zurück zum Zitat Abdulahad WH, Stegeman CA, van der Geld YM et al (2007) Functional defect of circulating regulatory CD4 T cells in patients with Wegener’s granulomatosis in remission. Arthritis Rheum 56:2080–2091PubMedCrossRef Abdulahad WH, Stegeman CA, van der Geld YM et al (2007) Functional defect of circulating regulatory CD4 T cells in patients with Wegener’s granulomatosis in remission. Arthritis Rheum 56:2080–2091PubMedCrossRef
19.
Zurück zum Zitat Venken K, Hellings N, Liblau R et al (2010) Disturbed regulatory T cell homeostasis in multiple sclerosis. Trends Mol Med 16:58–68PubMedCrossRef Venken K, Hellings N, Liblau R et al (2010) Disturbed regulatory T cell homeostasis in multiple sclerosis. Trends Mol Med 16:58–68PubMedCrossRef
20.
Zurück zum Zitat Wright GP, Notley CA, Xue SA et al (2009) Adoptive therapy with redirected primary regulatory T cells results in antigen-specific suppression of arthritis. Proc Natl Acad Sci USA 106:19078–19083PubMedCrossRef Wright GP, Notley CA, Xue SA et al (2009) Adoptive therapy with redirected primary regulatory T cells results in antigen-specific suppression of arthritis. Proc Natl Acad Sci USA 106:19078–19083PubMedCrossRef
21.
Zurück zum Zitat Morgan ME, Flierman R, van Duivenvoorde LM et al (2005) Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+ regulatory T cells. Arthritis Rheum 52:2212–2221PubMedCrossRef Morgan ME, Flierman R, van Duivenvoorde LM et al (2005) Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+ regulatory T cells. Arthritis Rheum 52:2212–2221PubMedCrossRef
22.
Zurück zum Zitat Bettelli E, Carrier Y, Gao W et al (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:235–238PubMedCrossRef Bettelli E, Carrier Y, Gao W et al (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:235–238PubMedCrossRef
23.
Zurück zum Zitat Kurts C (2008) Th17 cells: a third subset of CD4+ T effector cells involved in organ-specific autoimmunity. Nephrol Dial Transplant 23:816–819PubMedCrossRef Kurts C (2008) Th17 cells: a third subset of CD4+ T effector cells involved in organ-specific autoimmunity. Nephrol Dial Transplant 23:816–819PubMedCrossRef
24.
Zurück zum Zitat Wilson NJ, Boniface K, Chan JR et al (2007) Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 8:950–957PubMedCrossRef Wilson NJ, Boniface K, Chan JR et al (2007) Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 8:950–957PubMedCrossRef
25.
Zurück zum Zitat Fontenot JD, Gavin MA, Rudensky AY (2003) Foxp3 programs the development and function of CD4+ CD25+ regulatory T cells. Nat Immunol 4:330–336PubMedCrossRef Fontenot JD, Gavin MA, Rudensky AY (2003) Foxp3 programs the development and function of CD4+ CD25+ regulatory T cells. Nat Immunol 4:330–336PubMedCrossRef
26.
Zurück zum Zitat Acosta-Rodriguez EV, Napoletani G, Lanzavecchia A et al (2007) Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 8:942PubMedCrossRef Acosta-Rodriguez EV, Napoletani G, Lanzavecchia A et al (2007) Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 8:942PubMedCrossRef
Metadaten
Titel
Disturbed Th17/Treg balance in patients with rheumatoid arthritis
verfasst von
Qian Niu
Bei Cai
Zhuo-chun Huang
Yun-ying Shi
Lan-lan Wang
Publikationsdatum
01.09.2012
Verlag
Springer-Verlag
Erschienen in
Rheumatology International / Ausgabe 9/2012
Print ISSN: 0172-8172
Elektronische ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-011-1984-x

Weitere Artikel der Ausgabe 9/2012

Rheumatology International 9/2012 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.