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Published in: Journal of Clinical Immunology 4/2013

01-05-2013 | Original Research

Th22, but not Th17 Might be a Good Index to Predict the Tissue Involvement of Systemic Lupus Erythematosus

Authors: Xu-yan Yang, Hui-ying Wang, Xiao-ying Zhao, Li-juan Wang, Qing-hua Lv, Qing-qing Wang

Published in: Journal of Clinical Immunology | Issue 4/2013

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Abstract

Purpose

T-helper (Th) cells abnormalities are considered to be associated with the pathogenesis of Systemic lupus erythematosus (SLE). Recently, The Th22 cells have been identified and implicated in the pathogenesis of autoimmune diseases such as Rheumatoid arthritis (RA), although therir role in Systemic lupus erythematosus (SLE) remains unclear. The present study intends to investigate their roles in SLE.

Methods

Clinical data were collected in 65 SLE patients and 30 healthy controls. The patients were divided into active and inactive groups. CD4+IFN-γIL-17IL-22+Tcells (Th22 cells),CD4+ IFN-γIL-22IL-17+T cells (Th17 cells),and CD4+ IFN-γ+ (Th1 cells) were assayed by flow cytometry. Serum interleukin-22 (IL-22) and IL-17 levels were measured by enzyme-linked immunosorbent assay.

Results

The main observation focused on increased Th22 cells in patients with sole lupus skin disease and decreased Th22 cells in patients with sole lupus nephritis. Likewise, concentrations of serum IL-22 were increased in patients with sole lupus skin disease, and decreased in patients with sole lupus nephritis. Additionally, there was a positive correlation between the percentage of Th22 cells and IL-22 production. The percentage of Th17 cells or concentration of serum IL-17 correlated positively with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).

Conclusion

Th22 seems to be a more significant index to predict the tissue involvement of SLE than Th17, although Th17 may play a role in the activity of SLE.
Literature
1.
go back to reference Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–73.PubMedCrossRef Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–73.PubMedCrossRef
2.
go back to reference Dolhain RJ, van der Heiden AN, ter Haar NT, Breedveld FC, Miltenburg AM. Shift toward T lymphocytes with a T helper 1 cytokine-secretion profile in the joints of patients with rheumatoid arthritis. Arthritis Rheum. 1996;39:1961–9.PubMedCrossRef Dolhain RJ, van der Heiden AN, ter Haar NT, Breedveld FC, Miltenburg AM. Shift toward T lymphocytes with a T helper 1 cytokine-secretion profile in the joints of patients with rheumatoid arthritis. Arthritis Rheum. 1996;39:1961–9.PubMedCrossRef
3.
go back to reference Wedderburn LR, Robinson N, Patel A, Varsani H, Woo P. Selective recruitment of polarized T cells expressing CCR5 and CXCR3 to the inflamed joints of children with juvenile idiopathic arthritis. Arthritis Rheum. 2000;43:765–74.PubMedCrossRef Wedderburn LR, Robinson N, Patel A, Varsani H, Woo P. Selective recruitment of polarized T cells expressing CCR5 and CXCR3 to the inflamed joints of children with juvenile idiopathic arthritis. Arthritis Rheum. 2000;43:765–74.PubMedCrossRef
4.
go back to reference Weaver CT, Harrington LE, Mangan PR, Gavrieli M, Murphy KM. Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity. 2006;24:677–88.PubMedCrossRef Weaver CT, Harrington LE, Mangan PR, Gavrieli M, Murphy KM. Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity. 2006;24:677–88.PubMedCrossRef
5.
go back to reference Mangan PR, Harrington LE, O’Quinn DB, Helms WS, Bullard DC, Elson CO, et al. Transforming growth factor-β induces development of the TH17 lineage. Nature. 2006;441:231–4.PubMedCrossRef Mangan PR, Harrington LE, O’Quinn DB, Helms WS, Bullard DC, Elson CO, et al. Transforming growth factor-β induces development of the TH17 lineage. Nature. 2006;441:231–4.PubMedCrossRef
6.
go back to reference Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, 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;6:1123–32.PubMedCrossRef Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, 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;6:1123–32.PubMedCrossRef
7.
go back to reference Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6:1133–41.PubMedCrossRef Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6:1133–41.PubMedCrossRef
8.
go back to reference Bettelli E, Korn T, Oukka M, Kuchroo VK. Induction and effector functions of TH17 cells. Nature. 2008;453:1051–7.PubMedCrossRef Bettelli E, Korn T, Oukka M, Kuchroo VK. Induction and effector functions of TH17 cells. Nature. 2008;453:1051–7.PubMedCrossRef
9.
go back to reference Miossec P, Korn T, Kuchroo VK. Interleukin-17 and type 17 helper T cells. New Engl J Med. 2009;361:888–98.PubMedCrossRef Miossec P, Korn T, Kuchroo VK. Interleukin-17 and type 17 helper T cells. New Engl J Med. 2009;361:888–98.PubMedCrossRef
10.
go back to reference Dardalhon V, Korn T, Kuchroo VK, Anderson AC. Role of Th1 and Th17 cells in organ-specific autoimmunity. J Autoimmun. 2008;31:252–6.PubMedCrossRef Dardalhon V, Korn T, Kuchroo VK, Anderson AC. Role of Th1 and Th17 cells in organ-specific autoimmunity. J Autoimmun. 2008;31:252–6.PubMedCrossRef
11.
go back to reference Sullivan KE, Piliero LM, Dharia T, Goldman D, Petri MA. 3- polymorphisms of ETS1 are associated with different clinical phenotypes in SLE. Hum Mutat. 2000;16:49–53.PubMedCrossRef Sullivan KE, Piliero LM, Dharia T, Goldman D, Petri MA. 3- polymorphisms of ETS1 are associated with different clinical phenotypes in SLE. Hum Mutat. 2000;16:49–53.PubMedCrossRef
12.
go back to reference Wong CK, Ho CY, Li EK, Lam CW. Elevation of proinflammatory Cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus. Lupus. 2000;9:589–93.PubMedCrossRef Wong CK, Ho CY, Li EK, Lam CW. Elevation of proinflammatory Cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus. Lupus. 2000;9:589–93.PubMedCrossRef
13.
go back to reference Hsu HC, Yang P, Wang J, Wu Q, Myers R, Chen J, et al. Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat Immunol. 2008;9:166–75.PubMedCrossRef Hsu HC, Yang P, Wang J, Wu Q, Myers R, Chen J, et al. Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat Immunol. 2008;9:166–75.PubMedCrossRef
14.
go back to reference Duhen T, Geiger R, Jarrossay D, Lanzavecchia A, Sallusto F. Production of interleukin 22 but not interleukin17 by a subset of human skin-homing memory T cells. Nat Immunol. 2009;10:857–63.PubMedCrossRef Duhen T, Geiger R, Jarrossay D, Lanzavecchia A, Sallusto F. Production of interleukin 22 but not interleukin17 by a subset of human skin-homing memory T cells. Nat Immunol. 2009;10:857–63.PubMedCrossRef
15.
go back to reference Eyerich S, Eyerich K, Pennino D, Carbone T, Nasorri F, Pallotta S, et al. Th22 cells represent a distinct human T cell subsetinvolved in epidermal immunity and remodeling. J Clin Invest. 2009;119:3573–85.PubMed Eyerich S, Eyerich K, Pennino D, Carbone T, Nasorri F, Pallotta S, et al. Th22 cells represent a distinct human T cell subsetinvolved in epidermal immunity and remodeling. J Clin Invest. 2009;119:3573–85.PubMed
16.
go back to reference Trifari S, Kaplan C, Tran E, Crellin N, Spits H. Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells. Nat Immunol. 2009;10:864–71.PubMedCrossRef Trifari S, Kaplan C, Tran E, Crellin N, Spits H. Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells. Nat Immunol. 2009;10:864–71.PubMedCrossRef
17.
go back to reference Dumoutier L, Louahed J, Renauld JC. Cloning and characterization of IL-10-related Tcell-derived inducible factor (IL-TIF), a novel cytokine structurally related to IL-10 and inducible by IL-9. J Immunol. 2000;164:1814–9.PubMed Dumoutier L, Louahed J, Renauld JC. Cloning and characterization of IL-10-related Tcell-derived inducible factor (IL-TIF), a novel cytokine structurally related to IL-10 and inducible by IL-9. J Immunol. 2000;164:1814–9.PubMed
18.
go back to reference Zhang N, Pan H-F, Ye D-Q. Th22 in inflammatory and autoimmune disease: prospects for therapeutic intervention. Mol Cell Biochem. 2011;353:41–6.PubMedCrossRef Zhang N, Pan H-F, Ye D-Q. Th22 in inflammatory and autoimmune disease: prospects for therapeutic intervention. Mol Cell Biochem. 2011;353:41–6.PubMedCrossRef
19.
go back to reference Kagami S, Rizzo HL, Lee JJ, Koguchi Y, Blauvelt A. Circulating Th17, Th22, and Th1 cells are increased in psoriasis. J Invest Dermatol. 2010;130:1373–83.PubMedCrossRef Kagami S, Rizzo HL, Lee JJ, Koguchi Y, Blauvelt A. Circulating Th17, Th22, and Th1 cells are increased in psoriasis. J Invest Dermatol. 2010;130:1373–83.PubMedCrossRef
20.
go back to reference Truchetet ME, Brembillal NC, Montanari E, et al. Increased frequency of circulating Th22 in addition to Th17 and Th2 lymphocytes in systemic sclerosis: association with interstitial lung disease. Arthritis Res Ther. 2011;13:R166.PubMedCrossRef Truchetet ME, Brembillal NC, Montanari E, et al. Increased frequency of circulating Th22 in addition to Th17 and Th2 lymphocytes in systemic sclerosis: association with interstitial lung disease. Arthritis Res Ther. 2011;13:R166.PubMedCrossRef
21.
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;60:1647–56.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;60:1647–56.PubMedCrossRef
22.
go back to reference Zhang L, Li JM, Liu XG, et al. Elevated Th22 Cells Correlated with Th17 Cells in Patients with Rheumatoid Arthritis. J Clin Immunol. 2011;31:606–14.PubMedCrossRef Zhang L, Li JM, Liu XG, et al. Elevated Th22 Cells Correlated with Th17 Cells in Patients with Rheumatoid Arthritis. J Clin Immunol. 2011;31:606–14.PubMedCrossRef
23.
go back to reference Ikeuchi H, Kuroiwa T, Hiramatsu N, et al. Expression of interleukin-22 in rheumatoid arthritis: potential role as a proinflammatory cytokine. Arthritis Rheum. 2005;52(4):1037–46.PubMedCrossRef Ikeuchi H, Kuroiwa T, Hiramatsu N, et al. Expression of interleukin-22 in rheumatoid arthritis: potential role as a proinflammatory cytokine. Arthritis Rheum. 2005;52(4):1037–46.PubMedCrossRef
24.
go back to reference Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40:1725.PubMedCrossRef Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40:1725.PubMedCrossRef
25.
go back to reference Gladman DD, Ibanez D, Urowitz MB. Systemic Lupus Erythematosus Disease Activity Index 2000. J Rheumatol. 2002;29:288–91.PubMed Gladman DD, Ibanez D, Urowitz MB. Systemic Lupus Erythematosus Disease Activity Index 2000. J Rheumatol. 2002;29:288–91.PubMed
26.
go back to reference Pan HF, Fnag XH, Wu GC, et al. Anti-neutrophil cytoplasmic antibodies in new-onset Systemic Lupus Erythematosus and lupus nephritis. Inflammation. 2008;31:260–5.PubMedCrossRef Pan HF, Fnag XH, Wu GC, et al. Anti-neutrophil cytoplasmic antibodies in new-onset Systemic Lupus Erythematosus and lupus nephritis. Inflammation. 2008;31:260–5.PubMedCrossRef
27.
go back to reference Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R. IL-22 increases the innate immunity of tissues. Immunity. 2004;21:241–54.PubMedCrossRef Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R. IL-22 increases the innate immunity of tissues. Immunity. 2004;21:241–54.PubMedCrossRef
28.
go back to reference Wolk K, Witte E, Witte K, Warszawska K, Sabat R. Biology of interleukin-22. Semin Immunopathol. 2010;32:17–31.PubMedCrossRef Wolk K, Witte E, Witte K, Warszawska K, Sabat R. Biology of interleukin-22. Semin Immunopathol. 2010;32:17–31.PubMedCrossRef
29.
go back to reference Zenewicz LA, Yancopoulos GD, Valenzuela DM, Murphy AJ, Stevens S, Flavell RA. Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity. 2008;29:947–57.PubMedCrossRef Zenewicz LA, Yancopoulos GD, Valenzuela DM, Murphy AJ, Stevens S, Flavell RA. Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity. 2008;29:947–57.PubMedCrossRef
30.
go back to reference Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J, et al. Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature. 2007;445:648–51.PubMedCrossRef Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J, et al. Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature. 2007;445:648–51.PubMedCrossRef
31.
go back to reference Ma HL, Liang S, Li J, Napierata L, Brown T, Benoit S, et al. IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. J Clin Invest. 2008;118:597–607.PubMed Ma HL, Liang S, Li J, Napierata L, Brown T, Benoit S, et al. IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. J Clin Invest. 2008;118:597–607.PubMed
32.
go back to reference Wolk K, Haugen HS, Xu W, Witte E, Waggie K, Anderson M, et al. IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-gamma are not. J Mol Med. 2009;87(5):523–36.PubMedCrossRef Wolk K, Haugen HS, Xu W, Witte E, Waggie K, Anderson M, et al. IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-gamma are not. J Mol Med. 2009;87(5):523–36.PubMedCrossRef
33.
go back to reference Kolb H, Kolb-Bachofen V. Nitric oxide: a pathogenetic factor in autoimmunity. Immunol Today. 1992;13:157–1601.PubMedCrossRef Kolb H, Kolb-Bachofen V. Nitric oxide: a pathogenetic factor in autoimmunity. Immunol Today. 1992;13:157–1601.PubMedCrossRef
34.
go back to reference Jonuleit H, Dnop J, End AH. Cytokines and their effects on maturation, differentiation and migration of dendratic cells. Arch Dermatol Res. 1996;289:1.PubMedCrossRef Jonuleit H, Dnop J, End AH. Cytokines and their effects on maturation, differentiation and migration of dendratic cells. Arch Dermatol Res. 1996;289:1.PubMedCrossRef
35.
go back to reference Fairhurst AM, Mathian A, Connolly JE, et al. Systemic TNF-αdrives kidney nephritis in B6.Sle123 mice. Eur J Immunol. 2008;38(7):1948–60.PubMedCrossRef Fairhurst AM, Mathian A, Connolly JE, et al. Systemic TNF-αdrives kidney nephritis in B6.Sle123 mice. Eur J Immunol. 2008;38(7):1948–60.PubMedCrossRef
36.
go back to reference Jacob CO, Fronek Z, Lewis GD, et al. Heritable major histocompatibility complex class II-associated difference in production of tumor necrosis factor alpha: relevance to genetic predisposition to systemic lupus erythematosus. Proc Nacl Acad Sci U S A. 1990;87:1233–7.CrossRef Jacob CO, Fronek Z, Lewis GD, et al. Heritable major histocompatibility complex class II-associated difference in production of tumor necrosis factor alpha: relevance to genetic predisposition to systemic lupus erythematosus. Proc Nacl Acad Sci U S A. 1990;87:1233–7.CrossRef
37.
go back to reference Doreau A, Belot A, Bastid J, Riche B, Trescol-Biemont MC, Ranchin B, et al. Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat Immunol. 2009;10:778–85.PubMedCrossRef Doreau A, Belot A, Bastid J, Riche B, Trescol-Biemont MC, Ranchin B, et al. Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat Immunol. 2009;10:778–85.PubMedCrossRef
38.
go back to reference Dong G, Ye R, Shi W, et al. IL-17 induces autoantibody overproduction and peripheral blood mononuclear cell overexpression of IL-6 in lupus nephritis patients. Chin Med J (Engl). 2003;116:543–8. Dong G, Ye R, Shi W, et al. IL-17 induces autoantibody overproduction and peripheral blood mononuclear cell overexpression of IL-6 in lupus nephritis patients. Chin Med J (Engl). 2003;116:543–8.
39.
go back to reference Ma J, Yu J, Tao X, et al. The imbalance between regulatory and IL-17-secreting CD4+ T cells in lupus patients. Clin Rheumatol. 2010;29:1251–8.PubMedCrossRef Ma J, Yu J, Tao X, et al. The imbalance between regulatory and IL-17-secreting CD4+ T cells in lupus patients. Clin Rheumatol. 2010;29:1251–8.PubMedCrossRef
40.
go back to reference Henriques A, Ines L, Couto M, et al. Frequency and functional activity of Th17, Tcl7 and other T-cell subsets in Systemic Lupus Erythematosus. Cell Immunol. 2010;264:97–103.PubMedCrossRef Henriques A, Ines L, Couto M, et al. Frequency and functional activity of Th17, Tcl7 and other T-cell subsets in Systemic Lupus Erythematosus. Cell Immunol. 2010;264:97–103.PubMedCrossRef
41.
go back to reference Funauclli MS, Ikoma H, Enomoto, et al. Decreased Thl-like and increased Th2-like cells in systemic lupus erythematosus. Scand J Rheumatol. 1998;27(3):p219–24.CrossRef Funauclli MS, Ikoma H, Enomoto, et al. Decreased Thl-like and increased Th2-like cells in systemic lupus erythematosus. Scand J Rheumatol. 1998;27(3):p219–24.CrossRef
42.
go back to reference Chang DM, Su WL, Chu SJ. The expression and significance of intracellular T helper cytokines in systemic 1upus erythematosus. Immunol Invest. 2002;31(1):1–12.PubMedCrossRef Chang DM, Su WL, Chu SJ. The expression and significance of intracellular T helper cytokines in systemic 1upus erythematosus. Immunol Invest. 2002;31(1):1–12.PubMedCrossRef
Metadata
Title
Th22, but not Th17 Might be a Good Index to Predict the Tissue Involvement of Systemic Lupus Erythematosus
Authors
Xu-yan Yang
Hui-ying Wang
Xiao-ying Zhao
Li-juan Wang
Qing-hua Lv
Qing-qing Wang
Publication date
01-05-2013
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 4/2013
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-013-9878-1

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