Skip to main content
Top
Published in: Inflammation 5/2018

01-10-2018 | ORIGINAL ARTICLE

Changes of Treg/Th17 Ratio in Spleen of Acute Gouty Arthritis Rat Induced by MSU Crystals

Authors: Xiao-Juan Dai, Jin-Hui Tao, Xuan Fang, Yuan Xia, Xiao-Mei Li, Yi-Ping Wang, Xiang-Pei Li

Published in: Inflammation | Issue 5/2018

Login to get access

Abstract

Acute gouty arthritis is the inflammation of joint tissues in the acute form due to the deposition of monosodium urate (MSU) crystals. Regulatory T cells (Tregs) and Th17 cells play an important role in the development and progression of inflammatory diseases. However, the expression and role of Tregs and Th17 cells are not clear in this disease. Here, we investigated the changes of Tregs, Th17 cells, and Treg/Th17 ratio in spleen, as well as the inflammatory cytokines in blood and joint tissue pathology in acute gouty arthritis rat induced by MSU. We found that both the percentages of Tregs and Th17 cells in spleen increased at an early stage (6 h). Tregs decreased at 12 and 24 h, and rise again at 48 and 72 h. However, Th17 cells reached its peak at 24 h, and then decreased after 48 h. Treg/Th17 ratio showed an initial decrease and then increase, and further reached its minimum value at 24 h. But the ratios of Treg/Th17at all times were lower than that of normal control. The level of serum cytokines (IL-1β, IL-6, IL-17, TNF-α, and IL-10) showed an opposite trend to Treg/Th17 ratio, except the level of TGF-β1 was similar to Tregs. In summary, Tregs and Th17 cells in spleen changed over time during the development of acute gouty arthritis. Decrease of Treg/Th17 ratio was consistent with inflammation development in the joints, suggesting that Treg/Th17 imbalance may involve in pathogenesis of acute gouty arthritis.
Literature
1.
go back to reference Murunikkara, V., and M. Rasool. 2014. Trikatu, a herbal compound that suppresses monosodium urate crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. Cell Biochemistry & Function 32 (1): 106–114.CrossRef Murunikkara, V., and M. Rasool. 2014. Trikatu, a herbal compound that suppresses monosodium urate crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. Cell Biochemistry & Function 32 (1): 106–114.CrossRef
2.
go back to reference Schlesinger, N., and R.G. Thiele. 2010. The pathogenesis of bone erosions in gouty arthritis. Annals of the Rheumatic Diseases 69 (11): 1907–1912.CrossRefPubMed Schlesinger, N., and R.G. Thiele. 2010. The pathogenesis of bone erosions in gouty arthritis. Annals of the Rheumatic Diseases 69 (11): 1907–1912.CrossRefPubMed
3.
go back to reference Sakaguchi, S., M. Miyara, C.M. Costantino, and D.A. Hafler. 2010. Foxp3+ regulatory T cells in the human immune system. Nature Reviews Immunology 10 (7): 490–500.CrossRefPubMed Sakaguchi, S., M. Miyara, C.M. Costantino, and D.A. Hafler. 2010. Foxp3+ regulatory T cells in the human immune system. Nature Reviews Immunology 10 (7): 490–500.CrossRefPubMed
4.
go back to reference Piccirillo, C.A., E. D’Hennezel, E. Sgouroudis, and E. Yurchenko. 2008. Cd4+Foxp3+ regulatory T cells in the control of autoimmunity: in vivo veritas. Current Opinion in Immunology 20 (6): 655–662.CrossRefPubMed Piccirillo, C.A., E. D’Hennezel, E. Sgouroudis, and E. Yurchenko. 2008. Cd4+Foxp3+ regulatory T cells in the control of autoimmunity: in vivo veritas. Current Opinion in Immunology 20 (6): 655–662.CrossRefPubMed
6.
go back to reference Zhou, L., J.E. Lopes, M.M. Chong, I.I. Ivanov, R. Min, G.D. Victora, et al. 2008. TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function. Nature 453: 236–240.CrossRefPubMedPubMedCentral Zhou, L., J.E. Lopes, M.M. Chong, I.I. Ivanov, R. Min, G.D. Victora, et al. 2008. TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function. Nature 453: 236–240.CrossRefPubMedPubMedCentral
7.
go back to reference Coderre, T.J., and P.D. Wall. 1987. Ankle joint urate arthritis (AJUA) in rats: an alternative animal model of arthritis to that produced by Freund’s adjuvant. Pain 28 (3): 379–393.CrossRefPubMed Coderre, T.J., and P.D. Wall. 1987. Ankle joint urate arthritis (AJUA) in rats: an alternative animal model of arthritis to that produced by Freund’s adjuvant. Pain 28 (3): 379–393.CrossRefPubMed
8.
go back to reference Park, J.S., Y. Oh, O. Park, C.A. Foss, S.M. Lim, D.G. Jo, et al. 2017. Pegylated trail ameliorates experimental inflammatory arthritis by regulation of Th17 cells and regulatory T cells. Journal of Controlled Release 267: 163–171.CrossRefPubMed Park, J.S., Y. Oh, O. Park, C.A. Foss, S.M. Lim, D.G. Jo, et al. 2017. Pegylated trail ameliorates experimental inflammatory arthritis by regulation of Th17 cells and regulatory T cells. Journal of Controlled Release 267: 163–171.CrossRefPubMed
9.
go back to reference Hartmann, P., A. Szabó, G. Eros, D. Gurabi, G. Horváth, I. Németh, et al. 2009. Anti-inflammatory effects of phosphatidylcholine in neutrophil leukocyte-dependent acute arthritis in rats. European Journal of Pharmacology 622 (1–3): 58–64.CrossRefPubMed Hartmann, P., A. Szabó, G. Eros, D. Gurabi, G. Horváth, I. Németh, et al. 2009. Anti-inflammatory effects of phosphatidylcholine in neutrophil leukocyte-dependent acute arthritis in rats. European Journal of Pharmacology 622 (1–3): 58–64.CrossRefPubMed
10.
go back to reference Fasching, P., M. Stradner, W. Graninger, C. Dejaco, and J. Fessler. 2017. Therapeutic potential of targeting the Th17/Treg axis in autoimmune disorders. Molecules 22 (1): 134.CrossRef Fasching, P., M. Stradner, W. Graninger, C. Dejaco, and J. Fessler. 2017. Therapeutic potential of targeting the Th17/Treg axis in autoimmune disorders. Molecules 22 (1): 134.CrossRef
11.
go back to reference An, N., Y. Chen, C. Wang, C. Yang, Z.H. Wu, J. Xue, et al. 2017. Chloroquine autophagic inhibition rebalances Th17/Treg-mediated immunity and ameliorates systemic lupus erythematosus. Cellular Physiology & Biochemistry 44 (1): 412–422.CrossRef An, N., Y. Chen, C. Wang, C. Yang, Z.H. Wu, J. Xue, et al. 2017. Chloroquine autophagic inhibition rebalances Th17/Treg-mediated immunity and ameliorates systemic lupus erythematosus. Cellular Physiology & Biochemistry 44 (1): 412–422.CrossRef
12.
go back to reference Pesce, B., L. Soto, F. Sabugo, P. Wurmann, M. Cuchacovich, M.N. López, et al. 2013. Effect of interleukin-6 receptor blockade on the balance between regulatory T cells and T helper type 17 cells in rheumatoid arthritis patients. Clinical & Experimental Immunology 171 (3): 237–242.CrossRef Pesce, B., L. Soto, F. Sabugo, P. Wurmann, M. Cuchacovich, M.N. López, et al. 2013. Effect of interleukin-6 receptor blockade on the balance between regulatory T cells and T helper type 17 cells in rheumatoid arthritis patients. Clinical & Experimental Immunology 171 (3): 237–242.CrossRef
13.
go back to reference Tramontini, N., C. Huber, L.B. Ru, R.A. Terkeltaub, and K.S. Kilgore. 2004. Central role of complement membrane attack complex in monosodium urate crystal–induced neutrophilic rabbit knee synovitis. Arthritis & Rheumatology 50 (8): 2633–2639.CrossRef Tramontini, N., C. Huber, L.B. Ru, R.A. Terkeltaub, and K.S. Kilgore. 2004. Central role of complement membrane attack complex in monosodium urate crystal–induced neutrophilic rabbit knee synovitis. Arthritis & Rheumatology 50 (8): 2633–2639.CrossRef
14.
go back to reference Taylor, W.J., J. Fransen, T.L. Jansen, N. Dalbeth, H.R. Schumacher, M. Brown, et al. 2015. Study for updated gout classification criteria: identification of features to classify gout. Arthritis Care & Research 67 (9): 1304–1315.CrossRef Taylor, W.J., J. Fransen, T.L. Jansen, N. Dalbeth, H.R. Schumacher, M. Brown, et al. 2015. Study for updated gout classification criteria: identification of features to classify gout. Arthritis Care & Research 67 (9): 1304–1315.CrossRef
15.
go back to reference Nistala, K., H. Moncrieffe, K.R. Newton, H. Varsani, P. Hunter, and L.R. Wedderburn. 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 & Rheumatology 58 (3): 875–887.CrossRef Nistala, K., H. Moncrieffe, K.R. Newton, H. Varsani, P. Hunter, and L.R. Wedderburn. 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 & Rheumatology 58 (3): 875–887.CrossRef
16.
go back to reference Monte, K., C. Wilson, and F.F. Shih. 2008. Increased number and function of Foxp3 regulatory T cells during experimental arthritis. Arthritis and Rheumatism 58 (12): 3730–3741.CrossRefPubMedPubMedCentral Monte, K., C. Wilson, and F.F. Shih. 2008. Increased number and function of Foxp3 regulatory T cells during experimental arthritis. Arthritis and Rheumatism 58 (12): 3730–3741.CrossRefPubMedPubMedCentral
17.
go back to reference Belkaid, Y. 2007. Regulatory T cells and infection: a dangerous necessity. Nature Reviews Immunology 7 (11): 875–888.CrossRefPubMed Belkaid, Y. 2007. Regulatory T cells and infection: a dangerous necessity. Nature Reviews Immunology 7 (11): 875–888.CrossRefPubMed
18.
go back to reference Flores-García, Y., J.L. Rosales-Encina, V.H. Rosales-García, A.R. Satoskar, and P. Talamás-Rohana. 2013. Cd4+ cd25+ Foxp3+ Treg cells induced by rSSP4 derived from T. cruzi amastigotes increase parasitemia in an experimental Chagas disease model. BioMed Research International 2013 (1): 632436.PubMed Flores-García, Y., J.L. Rosales-Encina, V.H. Rosales-García, A.R. Satoskar, and P. Talamás-Rohana. 2013. Cd4+ cd25+ Foxp3+ Treg cells induced by rSSP4 derived from T. cruzi amastigotes increase parasitemia in an experimental Chagas disease model. BioMed Research International 2013 (1): 632436.PubMed
19.
go back to reference Manuscript, A., G. Schett, J.M. Dayer, B. Manger, F.A. Amaral, V.V. Costa, et al. 2015. Mechanisms of inflammation in gout. Rheumatology 12 (2): 1090–1096. Manuscript, A., G. Schett, J.M. Dayer, B. Manger, F.A. Amaral, V.V. Costa, et al. 2015. Mechanisms of inflammation in gout. Rheumatology 12 (2): 1090–1096.
20.
go back to reference Martinon, F., V. Pétrilli, A. Mayor, A. Tardivel, and J. Tschopp. 2006. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440 (7081): 237–241.CrossRefPubMed Martinon, F., V. Pétrilli, A. Mayor, A. Tardivel, and J. Tschopp. 2006. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440 (7081): 237–241.CrossRefPubMed
21.
go back to reference Acosta-Rodriguez, E.V., G. Napolitani, A. Lanzavecchia, and F. Sallusto. 2007. Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nature Immunology 8 (9): 942–949.CrossRefPubMed Acosta-Rodriguez, E.V., G. Napolitani, A. Lanzavecchia, and F. Sallusto. 2007. Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nature Immunology 8 (9): 942–949.CrossRefPubMed
22.
go back to reference Feldhoff, L.M., C.M. Rueda, M.E. Moreno-Fernandez, J. Sauer, C.M. Jackson, C.A. Chougnet, et al. 2017. IL-1beta induced HIF-1alpha inhibits the differentiation of human FOXP3(+) T cells. Scientific Reports 7: 465.CrossRefPubMedPubMedCentral Feldhoff, L.M., C.M. Rueda, M.E. Moreno-Fernandez, J. Sauer, C.M. Jackson, C.A. Chougnet, et al. 2017. IL-1beta induced HIF-1alpha inhibits the differentiation of human FOXP3(+) T cells. Scientific Reports 7: 465.CrossRefPubMedPubMedCentral
23.
go back to reference Kimura, A., and T. Kishimoto. 2010. IL-6: regulator of Treg/Th17 balance. European Journal of Immunology 40 (7): 1830–1835.CrossRefPubMed Kimura, A., and T. Kishimoto. 2010. IL-6: regulator of Treg/Th17 balance. European Journal of Immunology 40 (7): 1830–1835.CrossRefPubMed
24.
go back to reference Scanu, A., F. Oliviero, R. Ramonda, P. Frallonardo, J.M. Dayer, and L. Punzi. 2012. Cytokine levels in human synovial fluid during the different stages of acute gout: role of transforming growth factor β1 in the resolution phase. Annals of the Rheumatic Diseases 71 (4): 621–624.CrossRefPubMed Scanu, A., F. Oliviero, R. Ramonda, P. Frallonardo, J.M. Dayer, and L. Punzi. 2012. Cytokine levels in human synovial fluid during the different stages of acute gout: role of transforming growth factor β1 in the resolution phase. Annals of the Rheumatic Diseases 71 (4): 621–624.CrossRefPubMed
25.
go back to reference Jamshidian, A., V. Shaygannejad, A. Pourazar, S.H. Zarkeshesfahani, and M. Gharagozloo. 2013. Biased Treg/Th17 balance away from regulatory toward inflammatory phenotype in relapsed multiple sclerosis and its correlation with severity of symptoms. Journal of Neuroimmunology 262 (1–2): 106–112.CrossRefPubMed Jamshidian, A., V. Shaygannejad, A. Pourazar, S.H. Zarkeshesfahani, and M. Gharagozloo. 2013. Biased Treg/Th17 balance away from regulatory toward inflammatory phenotype in relapsed multiple sclerosis and its correlation with severity of symptoms. Journal of Neuroimmunology 262 (1–2): 106–112.CrossRefPubMed
26.
go back to reference Tu, Z., H. Xue, W. Chen, L. Cao, and W. Zhang. 2017. Changes of treg and Th17 cells as well as cytokines in children with acute bronchitis. Experimental & Therapeutic Medicine 14 (4): 3846–3850.CrossRef Tu, Z., H. Xue, W. Chen, L. Cao, and W. Zhang. 2017. Changes of treg and Th17 cells as well as cytokines in children with acute bronchitis. Experimental & Therapeutic Medicine 14 (4): 3846–3850.CrossRef
27.
go back to reference Abeles, A.M. 2015. Hyperuricemia, gout, and cardiovascular disease: an update. Current Rheumatology Reports 17 (3): 1–5.CrossRef Abeles, A.M. 2015. Hyperuricemia, gout, and cardiovascular disease: an update. Current Rheumatology Reports 17 (3): 1–5.CrossRef
Metadata
Title
Changes of Treg/Th17 Ratio in Spleen of Acute Gouty Arthritis Rat Induced by MSU Crystals
Authors
Xiao-Juan Dai
Jin-Hui Tao
Xuan Fang
Yuan Xia
Xiao-Mei Li
Yi-Ping Wang
Xiang-Pei Li
Publication date
01-10-2018
Publisher
Springer US
Published in
Inflammation / Issue 5/2018
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-018-0839-y

Other articles of this Issue 5/2018

Inflammation 5/2018 Go to the issue