Journal of the European Academy of Dermatology and Venereology

Volume 28, Issue 8 pp. 1079-1086

Original Article

The Imbalance of Th17 cells and CD4⁺CD25^highFoxp3⁺ Treg cells in patients with atopic dermatitis

L. Ma,

L. Ma

Department of Dermatology, Binzhou Medical University Hospital, Binzhou, China

L. Ma, H.-B. Xue and X.-H. Guan contributed equally to this work.Search for more papers by this author

H.-B. Xue,

Corresponding Author

H.-B. Xue

Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, Binzhou, China

L. Ma, H.-B. Xue and X.-H. Guan contributed equally to this work.Correspondence: H.-B. Xue. E-mail: [email protected]Search for more papers by this author

X.-H. Guan,

X.-H. Guan

State Key Department of Dermatology, Hospital of China Medical University, Shenyang, China

L. Ma, H.-B. Xue and X.-H. Guan contributed equally to this work.Search for more papers by this author

C.-M. Shu,

C.-M. Shu

Department of Dermatology, Binzhou Medical University Hospital, Binzhou, China

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F. Wang,

F. Wang

Department of Dermatology, Binzhou Medical University Hospital, Binzhou, China

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J.-H. Zhang,

J.-H. Zhang

Department of Dermatology, Binzhou Medical University Hospital, Binzhou, China

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R.-Z. An,

R.-Z. An

Department of Dermatology, Binzhou Medical University Hospital, Binzhou, China

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L. Ma,

L. Ma

Department of Dermatology, Binzhou Medical University Hospital, Binzhou, China

L. Ma, H.-B. Xue and X.-H. Guan contributed equally to this work.Search for more papers by this author

H.-B. Xue,

Corresponding Author

H.-B. Xue

Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, Binzhou, China

L. Ma, H.-B. Xue and X.-H. Guan contributed equally to this work.Correspondence: H.-B. Xue. E-mail: [email protected]Search for more papers by this author

X.-H. Guan,

X.-H. Guan

State Key Department of Dermatology, Hospital of China Medical University, Shenyang, China

L. Ma, H.-B. Xue and X.-H. Guan contributed equally to this work.Search for more papers by this author

C.-M. Shu,

C.-M. Shu

Department of Dermatology, Binzhou Medical University Hospital, Binzhou, China

Search for more papers by this author

F. Wang,

F. Wang

Department of Dermatology, Binzhou Medical University Hospital, Binzhou, China

Search for more papers by this author

J.-H. Zhang,

J.-H. Zhang

Department of Dermatology, Binzhou Medical University Hospital, Binzhou, China

Search for more papers by this author

R.-Z. An,

R.-Z. An

Department of Dermatology, Binzhou Medical University Hospital, Binzhou, China

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First published: 07 November 2013

https://doi.org/10.1111/jdv.12288

Citations: 69

Conflicts of interest

None declared.

Funding sources

None declared.

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Abstract

Background

Th17/Treg imbalance is involved in several autoimmune, inflammatory and allergic reactions. Nevertheless, the possible contribution of Th17/Treg imbalance in atopic dermatitis (AD) remains unknown.

Objective

To explore the possible role of Th17/Treg imbalance in AD.

Methods

Th17 and Treg cells percentage in peripheral blood mononuclear cells (PBMCs) and skin specimens, specific transcription factor retinoic acid-related orphan receptor (ROR)γt and Foxp3 mRNA levels in PBMCs, as well as Th17- and Treg-related cytokines mRNA levels in PBMCs, serum concentrations, and expression levels in PBMCs culture supernatant after recombinant Dermatophagoides pteronyssinus antigen stimulation were detected in AD patients. Controls included patients with psoriasis, allergic contact dermatitis (ACD) and healthy donors.

Results

Th17 cells percentage, RORγt, IL-17 and IL-23 levels in peripheral circulation of AD patients were significantly higher than those in ACD patients and healthy controls, but lower than those of psoriasis patients. Treg cells percentage, Foxp3 and TGF-β mRNA levels were reduced in AD patients compared with healthy controls, while there were no significant differences among AD, ACD and psoriasis patients. Th17 cells percentage, IL-17 and IL-23 levels were increased, while Treg cells percentage and TGF-β level were decreased in AD lesion and PBMCs culture supernatant respectively. There was a negative association between Th17 and Treg cells percentage in AD patients. AD severity score positively correlated with Th17 cells percentage and Th17/Treg ratio, while negatively correlated with Treg cells percentage. Serum IgE levels positively correlated with Th17/Treg ratio.

Conclusion

In AD, there exists an immune imbalance in Th17 and Treg cells, which may contribute to its pathogenesis and development.

References

1Ma L, Gao XH, Zhao LP et al. Brain-derived neurotrophic factor gene polymorphisms and serum levels in Chinese atopic dermatitis patients. J Eur Acad Dermatol Venereol 2009; 23: 1277–1281.
10.1111/j.1468-3083.2009.03308.x
CAS PubMed Web of Science® Google Scholar
2Ma L, Zhang L, Di ZH et al. Association analysis of filaggrin gene mutations and atopic dermatitis in Northern China. Br J Dermatol 2010; 162: 225–257.
10.1111/j.1365-2133.2009.09539.x
CAS PubMed Web of Science® Google Scholar
3Weaver CT, Hatton RD, Mangan PR, Harrington LE. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol 2007; 25: 821–852.
10.1146/annurev.immunol.25.022106.141557
CAS PubMed Web of Science® Google Scholar
4Bettelli E, Oukka M, Kuchroo VK. T(H)-17 cells in the circle of immunity and autoimmunity. Nat Immunol 2007; 8: 345–350.
10.1038/ni0407-345
CAS PubMed Web of Science® Google Scholar
5Furuzawa-Carballeda J, Vargas-Rojas MI, Cabral AR. Autoimmune inflammation from the Th17 perspective. Autoimmun Rev 2007; 6: 169–175.
10.1016/j.autrev.2006.10.002
CAS PubMed Web of Science® Google Scholar
6Langrish CL, Chen Y, Blumenschein WM et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005; 201: 233–240.
10.1084/jem.20041257
CAS PubMed Web of Science® Google Scholar
7McGeachy MJ, Cua DJ. Th17 cell differentiation: the long and winding road. Immunity 2008; 28: 445–453.
10.1016/j.immuni.2008.03.001
CAS PubMed Web of Science® Google Scholar
8Toussirot E. The IL23/Th17 pathway as a therapeutic target in chronic inflammatory diseases. Inflamm Allergy Drug Targets 2012; 11: 159–168.
10.2174/187152812800392805
CAS PubMed Google Scholar
9Sakaguchi S, Ono M, Setoguchi R et al. Foxp3 + CD25 + CD4 + natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol Rev 2006; 212: 8–27.
10.1111/j.0105-2896.2006.00427.x
CAS PubMed Web of Science® Google Scholar
10Gavin MA, Rasmussen JP, Fontenot JD et al. Foxp3-dependent programme of regulatory T-cell differentiation. Nature 2007; 445: 771–775.
10.1038/nature05543
CAS PubMed Web of Science® Google Scholar
11Sakaguchi S. Regulatory T cells: history and perspective. Methods Mol Biol 2011; 707: 3–17.
10.1007/978-1-61737-979-6_1
CAS PubMed Web of Science® Google Scholar
12Venuprasad K, Kong YC, Farrar MA. Control of Th2-mediated inflammation by regulatory T cells. Am J Pathol 2010; 177: 525–531.
10.2353/ajpath.2010.090936
CAS PubMed Web of Science® Google Scholar
13Samson M, Audia S, Janikashvili N et al. Brief report: inhibition of interleukin-6 function corrects Th17/Treg cell imbalance in patients with rheumatoid arthritis. Arthritis Rheum 2012; 64: 2499–2503.
10.1002/art.34477
CAS PubMed Web of Science® Google Scholar
14Furuhashi T, Saito C, Torii K, Nishida E, Yamazaki S, Morita A. Photo(chemo)therapy reduces circulating Th17 cells and restores circulating regulatory T cells in psoriasis. PLoS ONE 2013; 8: e54895.
10.1371/journal.pone.0054895
CAS PubMed Web of Science® Google Scholar
15Shi YH, Shi GC, Wan HY et al. Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with allergic asthma. Chin Med J (Engl) 2011; 124: 1951–1956.
CAS PubMed Web of Science® Google Scholar
16Koga C, Kabashima K, Shiraishi N, Kobayashi M, Tokura Y. Possible pathogenic role of Th17 cells for atopic dermatitis. J Invest Dermatol 2008; 128: 2625–2630.
10.1038/jid.2008.111
CAS PubMed Web of Science® Google Scholar
17Ma L, Xue HB, Guan XH et al. Possible role of Th17 cells and IL-17 in the pathogenesis of atopic dermatitis in northern China. J Dermatol Sci 2012; 68: 66–68.
10.1016/j.jdermsci.2012.07.009
CAS PubMed Web of Science® Google Scholar
18Lesiak A, Smolewski P, Sobolewska-Sztychny D, Sysa-Jedrzejowska A, Narbutt J. The role of T-regulatory cells and Toll-like receptors 2 and 4 in atopic dermatitis. Scand J Immunol 2012; 76: 405–410.
10.1111/j.1365-3083.2012.02739.x
CAS PubMed Web of Science® Google Scholar
19Verhagen J, Akdis M, Traidl-Hoffmann C et al. Absence of T-regulatory cell expression and function in atopic dermatitis skin. J Allergy Clin Immunol 2006; 117: 176–183.
10.1016/j.jaci.2005.10.040
CAS PubMed Web of Science® Google Scholar
20Rajka G, Langeland T. Grading of severity of atopic dermatitis. Acta Drm Venerol 1989; 144: 13–14.
PubMed Web of Science® Google Scholar
21 Severity scoring of atopic dermatitis: the SCORAD index. Consensus report of the European task force on atopic dermatitis. Dermatology 1993; 186: 23–31.
10.1159/000247298
PubMed Web of Science® Google Scholar
22Marie JC, Letterio JJ, Gavin M, Rudensky AY. TGF-beta l maintains suppressor function and Foxp3 expression in CD4 + CD25 + regulatory T cells. J Exp Med 2005; 201: 1061–1067.
10.1084/jem.20042276
CAS PubMed Web of Science® Google Scholar
23Evans HG, Suddason T, Jackson I, Taams LS, Lord GM. Optimal induction of T helper 17 cells in humans requires T cell receptor ligation in the context of Toll-like receptor-activated monocytes. Proc Natl Acad Sci USA 2007; 104: 17034–17039.
10.1073/pnas.0708426104
CAS PubMed Web of Science® Google Scholar
24Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F. Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 2007; 8: 942–949.
10.1038/ni1496
CAS PubMed Web of Science® Google Scholar
25Wilson NJ, Boniface K, Chan JR et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 2007; 8: 950–957.
10.1038/ni1497
CAS PubMed Web of Science® Google Scholar
26Zhou L, Lopes JE, Chong MM et al. TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 2008; 453: 236–240.
10.1038/nature06878
CAS PubMed Web of Science® Google Scholar
27Ichiyama K, Yoshida H, Wakabayashi Y et al. Foxp3 inhibits ROR gammat- mediated IL-17 mRNA transcription through direct interaction with ROR gammat. J Biol Chem 2008; 283: 17003–17008.
10.1074/jbc.M801286200
CAS PubMed Web of Science® Google Scholar
28Izcue A, Hue S, Buonocore S et al. Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis. Immunity 2008; 28: 559–570.
10.1016/j.immuni.2008.02.019
CAS PubMed Web of Science® Google Scholar
29Xystrakis E, Boswell SE, Hawrylowicz CM. T regulatory cells and the control of allergic disease. Expert Opin Biol Ther 2006; 6: 121–133.
10.1517/14712598.6.2.121
CAS PubMed Web of Science® Google Scholar
30Bellinghausen I, Klostermann B, Knop J, Saloga J. Human CD4 + CD25 + T cells derived from the majority of atopic donors are able to suppress TH1 and TH2 cytokine production. J Allergy Clin Immunol 2003; 111: 862–868.
10.1067/mai.2003.1412
CAS PubMed Web of Science® Google Scholar
31Patel DD. Escape from tolerance in the human X-1inked autoimmunity-allergic disregulatioo syndrome and the Scurfy mouse. J Clin Invest 2001; 107: 155–157.
10.1172/JCI11966
CAS PubMed Web of Science® Google Scholar
32Wakashin H, Hirose K, Maezawa Y et al. IL-23 and Th17 cells enhance Th2-cell-mediated eosinophilic airway inflammation in mice. Am J Respir Crit Care Med 2008; 178: 1023–1032.
10.1164/rccm.200801-086OC
CAS PubMed Web of Science® Google Scholar

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Volume28, Issue8

August 2014

Pages 1079-1086

The Imbalance of Th17 cells and CD4⁺CD25^highFoxp3⁺ Treg cells in patients with atopic dermatitis

Conflicts of interest

Funding sources

Abstract

Background

Objective

Methods

Results

Conclusion

References

Citing Literature

References

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The Imbalance of Th17 cells and CD4+CD25highFoxp3+ Treg cells in patients with atopic dermatitis

Conflicts of interest

Funding sources

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Background

Objective

Methods

Results

Conclusion

References

Citing Literature

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The Imbalance of Th17 cells and CD4⁺CD25^highFoxp3⁺ Treg cells in patients with atopic dermatitis