Down-regulation of Helios Expression in Tregs from Patients with Hypertension

Zhu-yue Chen , Feng Chen , Yan-ge Wang , Ding-hang Wang , Li-li Jang , Long-xian Cheng

Current Medical Science ›› 2018, Vol. 38 ›› Issue (1) : 58 -63.

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Current Medical Science ›› 2018, Vol. 38 ›› Issue (1) : 58 -63. DOI: 10.1007/s11596-018-1846-9
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Down-regulation of Helios Expression in Tregs from Patients with Hypertension

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Abstract

Regulatory T cells (Tregs) play a pivotal role in the pathological development of hypertension. Helios, a transcription factor from the Ikaros family, was recently reported to be a bona fide marker for natural Tregs or activated Tregs with suppression function, however, little has been known about its role in hypertension. This study was aimed to find whether Helios+ Tregs really play a vital role in hypertension. A total of 60 hypertension patients, and 46 normotension subjects were enrolled in this study. Frequencies of different Tregs subsets in peripheral blood were measured by flow cytometry. Plasma cytokine level was determined by ELISA. The mRNA expression of Foxp3 and Helios in purified CD4+ T cells was detected by RT-PCR. Proportion of CD4+Foxp3+Helios+ Tregs was decreased significantly in patients with hypertension (62.52%±1.18% vs. 71.89%±1.03%, P<0.01), and it was correlated with plasma level of IL-10 positively (a=0.505, P<0.05) and plasma level of IFN-gamma negatively (r=—0.551, P<0.05). The mRNA expression of Foxp3 (7.23±1.00 vs. 10.58±0.54, P<0.05) and Helios (8.47±0.95 vs. 15.52±2.0, P<0.05) was decreased in CD4+ T cells from patients with hypertension. Helios+ Tregs were decreased in patients with hypertension and may play a protective role in hypertension progression.

Keywords

hypertension / cardiovascular disease / regulatory T cells / Helios / Foxp3

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Zhu-yue Chen, Feng Chen, Yan-ge Wang, Ding-hang Wang, Li-li Jang, Long-xian Cheng. Down-regulation of Helios Expression in Tregs from Patients with Hypertension. Current Medical Science, 2018, 38(1): 58-63 DOI:10.1007/s11596-018-1846-9

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References

[1]

WHO Mediacenter. Cardiovascular diseases (CVDs) fact sheets, 2017

[2]

World Health Organization. Global Health Observatory (GHO) Data, 2015

[3]

MianMO, BarhoumiT, BrietM, et al. . Deficiency of T-regulatory cells exaggerates angiotensin IIinduced microvascular injury by enhancing immune responses. J Hypertens, 2016, 34(1): 97-108 PMID: 26630215

[4]

BarhoumiT, KasalDA, LiMW, et al. . T regulatory lymphocytes prevent angiotensin Il-induced hypertension and vascular injury. Hypertension, 2011, 57(3): 469-476 PMID: 21263125

[5]

MatrouguiK A, ElmageedZ, KassanM, et al. . Natural regulatory T cells control coronary arteriolar endothelial dysfunction in hypertensive mice. Am J Pathol, 2011, 178(1): 434-441 PMID: 21224080 PMCID: 3069876

[6]

SakaguchiS. Regulatory T cells: key controllers of immunologic self-tolerance. Cell, 2000, 101(5): 455-458 PMID: 10850488

[7]

BennettCL, ChristieJ, RamsdellF, et al. . The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet, 2001, 27(1): 20-21 PMID: 11137993

[8]

FantiniMC, BeckerC, MonteleoneG, et al. . Cutting edge: TGF-beta induces a regulatory phenotype in CD4+CD25-T cells through Foxp3 induction and down-regulation of Smad7. J Immunol, 2004, 172(9): 5149-5153 PMID: 15100250

[9]

AllanSE, CromeSQ, CrellinNK, et al. . Activationinduced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. Int Immunol, 2007, 19(4): 345-354 PMID: 17329235

[10]

TranDQ, RamseyH, ShevachEM. Induction of FOXP3 expression in naive human CD4+FOXP3 T cells by T-cell receptor stimulation is transforming growth factor-beta dependent but does not confer a regulatory phenotype. Blood, 2007, 110(8): 2983-2990 PMID: 17644734 PMCID: 2018674

[11]

VignaliDA, CollisonLW, WorkmanCJ. How regulatory T cells work. Nat Rev Immunol, 2008, 8(7): 523-532 PMID: 18566595 PMCID: 2665249

[12]

FontenotJD, RasmussenJP, WilliamsLM, et al. . Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity, 2005, 22(3): 329-341 PMID: 15780990

[13]

ThorntonAM, KortyPE, TranDQ, et al. . Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J Immunol, 2010, 184(7): 3433-3441 PMID: 20181882 PMCID: 3725574

[14]

RossEM, BourgesD, HoganTV, et al. . Helios defines T cells being driven to tolerance in the periphery and thymus. Eur J Immunol, 2014, 44(7): 2048-2058 PMID: 24740292

[15]

PLoS One, 2011, 6(6

[16]

GottschalkRA, CorseE, AllisonJP. Expression of Helios in peripherally induced Foxp3+ regulatory T cells. J Immunol, 2012, 1883): 976-980 PMID: 22198953

[17]

DaleySR, HuDY, GoodnowCC. Helios marks strongly autoreactive CD4+ T cells in two major waves of thymic deletion distinguished by induction of PD-1 or NF-kappaB. J Exp Med, 2013, 210(2): 269-285 PMID: 23337809 PMCID: 3570102

[18]

KimHJ, BarnitzRA, KreslavskyT, et al. . Stable inhibitory activity of regulatory T cells requires the transcription factor Helios. Science, 2015, 350(6258): 334-339 PMID: 26472910 PMCID: 4627635

[19]

PLoS One, 2011, 6(8

[20]

LiuC, GuanZ, ZhaoL, et al. . Elevated level of circulating CD4+Helios+FoxP3+ cells in primary Sjogren's syndrome patients. Mod Rheumatol, 2017, 274): 630-637 PMID: 27538522

[21]

KlocperkA, GrecovaJ, SismovaK, et al. . Helios expression in T-regulatory cells in patients with di George Syndrome. J Clin Immunol, 2014, 34(7): 864-870 PMID: 25008482

[22]

ChenX V, LugtM, SzabolcsP. Deficiency of Foxp3/Helios co-expressing regulatory T-cells correlates with clinical acitvity in autoimmunity (HUM7P.316). J Immunol, 2014, 192: 184.25

[23]

EllisonS, GabuniaK, KelemenSE, et al. . Attenuation of experimental atherosclerosis by interleukin-19. Arterioscler Thromb Vase Biol, 2013, 33(10): 2316-2324

[24]

SugimotoN, OidaT, HirotaK, et al. . Foxp3-dependent and -independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysis. Int Immunol, 2006, 18(8): 1197-1209 PMID: 16772372

[25]

TakatoriH, KawashimaH, MatsukiA, et al. . Helios enhances Treg cell function in cooperation with FoxP3. Arthritis Rheumatol, 2015, 67(6): 1491-1502 PMID: 25733061

[26]

LiL, WuCY. CD4+ CD25+ Treg cells inhibit human memory gammadelta T cells to produce IFN-y in response to M tuberculosis antigen ESAT-6. Blood, 2008, lll(12): 5629-5636

[27]

ShevachEM. Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity, 2009, 30(5): 636-645 PMID: 19464986

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