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CLC number: R562.25

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Received: 2023-10-17

Revision Accepted: 2024-05-08

Crosschecked: 2018-08-07

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Sheng-tao Zhao

https://orcid.org/0000-0002-7994-0059

Chang-zheng Wang

https://orcid.org/0000-0002-8991-1315

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Journal of Zhejiang University SCIENCE B 2018 Vol.19 No.9 P.663-673

http://doi.org/10.1631/jzus.B1700346


Regulatory T cells and asthma


Author(s):  Sheng-tao Zhao, Chang-zheng Wang

Affiliation(s):  Institute of Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China; more

Corresponding email(s):   czwang@netease.com

Key Words:  Regulatory T cell, Asthma, Transforming growth factor β, (TGF-β, ), Interleukin 10 (IL-10), IL-35


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Sheng-tao Zhao, Chang-zheng Wang. Regulatory T cells and asthma[J]. Journal of Zhejiang University Science B, 2018, 19(9): 663-673.

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T1 - Regulatory T cells and asthma
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Abstract: 
asthma is a chronic disease of airway inflammation due to excessive T helper cell type 2 (Th2) response. Present treatment based on inhalation of synthetic glucocorticoids can only control Th2-driven chronic eosinophilic inflammation, but cannot change the immune tolerance of the body to external allergens. regulatory T cells (Tregs) are the main negative regulatory cells of the immune response. Tregs play a great role in regulating allergic, autoimmune, graft-versus-host responses, and other immune responses. In this review, we will discuss the classification and biological characteristics, the established immunomodulatory mechanisms, and the characteristics of induced differentiation of Tregs. We will also discuss the progress of Tregs in the field of asthma. We believe that further studies on the regulatory mechanisms of Tregs will provide better treatments and control strategies for asthma.

调节性T细胞与哮喘

概要:哮喘是一种由于II型T辅助细胞(Th2)反应过度而引起的慢性气道炎症疾病.目前以吸入糖皮质激素为基础的治疗仅能控制Th2驱动的慢性嗜酸性炎症,但是不能改变机体对外界过敏原的免疫耐受状态.调节性T细胞(Tregs)是免疫应答的主要负调节细胞,Tregs在调节变态反应、自身免疫反应、移植物抗宿主反应和其他免疫反应中发挥着重要作用.在本文中,我们综述了Tregs的分类和生物学特性、免疫调节机制及诱导分化特性.我们也探讨了Tregs在哮喘领域的研究进展.我们相信,进一步对Tregs调控免疫反应机制的研究会为哮喘防控提供更好的治疗方案和策略.
关键词:调节性T细胞;哮喘;转变生长因子β(TGF-β);白介素10(IL-10);IL-35

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Abbas AK, Benoist C, Bluestone JA, et al., 2013. Regulatory T cells: recommendations to simplify the nomenclature. Nat Immunol, 14(4):307-308.

[2]Albert MH, Liu Y, Anasetti C, et al., 2005. Antigen-dependent suppression of alloresponses by Foxp3-induced regulatory T cells in transplantation. Eur J Immunol, 35(9):2598-2607.

[3]Baatjes AJ, Smith SG, Watson R, et al., 2015. T regulatory cell phenotypes in peripheral blood and bronchoalveolar lavage from non-asthmatic and asthmatic subjects. Clin Exp Allergy, 45(11):1654-1662.

[4]Bardel E, Larousserie F, Charlot-Rabiega P, et al., 2008. Human CD4+CD25+Foxp3+ regulatory T cells do not constitutively express IL-35. J Immunol, 181(10):6898-6905.

[5]Berker M, Frank LJ, Gessner AL, et al., 2017. Allergies-A T cells perspective in the era beyond the TH1/TH2 paradigm. Clin Immunol, 174:73-83.

[6]Burks AW, Calderon MA, Casale T, et al., 2013. Update on allergy immunotherapy: American Academy of Allergy, Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report. J Allergy Clin Immunol, 131(5):1288-1296.e3.

[7]Charbonnier LM, Wang S, Georgiev P, et al., 2015a. Control of peripheral tolerance by regulatory T cell-intrinsic Notch signaling. Nat Immunol, 16(11):1162-1173.

[8]Charbonnier LM, Janssen E, Chou J, et al., 2015b. Regulatory T-cell deficiency and immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like disorder caused by loss-of-function mutations in LRBA. J Allergy Clin Immunol, 135(1):217-227.e9.

[9]Collison LW, Workman CJ, Kuo TT, et al., 2007. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature, 450(7169):566-569.

[10]Deaglio S, Robson SC, 2011. Ectonucleotidases as regulators of purinergic signaling in thrombosis, inflammation, and immunity. Adv Pharmacol, 61:301-332.

[11]Deaglio S, Dwyer KM, Gao WD, et al., 2007. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med, 204(6):1257-1265.

[12]Delgoffe GM, Woo SR, Turnis ME, et al., 2013. Stability and function of regulatory T cells is maintained by a neuropilin-1-semaphorin-4a axis. Nature, 501(7466):252-256.

[13]Desreumaux P, Foussat A, Allez M, et al., 2012. Safety and efficacy of antigen-specific regulatory T-cell therapy for patients with refractory Crohn’s disease. Gastroenterology, 143(5):1207-1217.e2.

[14]Fu CL, Chuang YH, Chau LY, et al., 2006. Effects of adenovirus-expressing IL-10 in alleviating airway inflammation in asthma. J Gene Med, 8(12):1393-1399.

[15]Gambineri E, Torgerson TR, Ochs HD, 2003. Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis. Curr Opin Rheumatol, 15(4):430-435.

[16]Gondek DC, Lu LF, Quezada SA, et al., 2005. Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism. J Immunol, 174(4):1783-1786.

[17]Grossman WJ, Verbsky JW, Barchet W, et al., 2004. Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity, 21(4):589-601.

[18]Hansen G, McIntire JJ, Yeung VP, et al., 2000. CD4+ T helper cells engineered to produce latent TGF-β1 reverse allergen-induced airway hyperreactivity and inflammation. J Clin Invest, 105(1):61-70.

[19]Hartl D, Koller B, Mehlhorn AT, et al., 2007. Quantitative and functional impairment of pulmonary CD4+CD25hi regulatory T cells in pediatric asthma. J Allergy Clin Immunol, 119(5):1258-1266.

[20]Heederik D, von Mutius E, 2012. Does diversity of environmental microbial exposure matter for the occurrence of allergy and asthma? J Allergy Clin Immunol, 130(1):44-50.

[21]Hershey GK, Friedrich MF, Esswein LA, et al., 1997. The association of atopy with a gain-of-function mutation in the α subunit of the interleukin-4 receptor. N Engl J Med, 337(24):1720-1725.

[22]Jethwa H, Adami AA, Maher J, 2014. Use of gene-modified regulatory T-cells to control autoimmune and alloimmune pathology: is now the right time? Clin Immunol, 150(1):51-63.

[23]Jiang YQ, Zhao ST, Yang X, et al., 2015. Dll4 in the DCs isolated from OVA-sensitized mice is involved in Th17 differentiation inhibition by 1,25-dihydroxyvitamin D3 in vitro. J Asthma, 52(10):989-995.

[24]Joetham A, Schedel M, O'Connor BP, et al., 2017. Inducible and naturally occurring regulatory T cells enhance lung allergic responses through divergent transcriptional pathways. J Allergy Clin Immunol, 139(4):1331-1342.

[25]John M, Lim S, Seybold J, et al., 1998. Inhaled corticosteroids increase interleukin-10 but reduce macrophage inflammatory protein-1α, granulocyte-macrophage colony-stimulating factor, and interferon-γ release from alveolar macrophages in asthma. Am J Respir Crit Care Med, 157(1):256-262.

[26]Jordan MS, Boesteanu A, Reed AJ, et al., 2001. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat Immunol, 2(4):301-306.

[27]Kanamori M, Nakatsukasa H, Okada M, et al., 2016. Induced regulatory T cells: their development, stability, and applications. Trends Immunol, 37(11):803-811.

[28]Kitani A, Fuss I, Nakamura K, et al., 2003. Transforming growth factor (TGF)-β1-producing regulatory T cells induce Smad-mediated interleukin 10 secretion that facilitates coordinated immunoregulatory activity and amelioration of TGF-β1-mediated fibrosis. J Exp Med, 198(8):1179-1188.

[29]Klatka M, Kaszubowska L, Grywalska E, et al., 2014. Treatment of Graves’ disease with methimazole in children alters the proliferation of Treg cells and CD3+ T lymphocytes. Folia Histochem Cytobiol, 52(1):69-77.

[30]Koch MA, Thomas KR, Perdue NR, et al., 2012. T-bet+ Treg cells undergo abortive Th1 cell differentiation due to impaired expression of IL-12 receptor β2. Immunity, 37(3):501-510.

[31]Komatsu N, Mariotti-Ferrandiz ME, Wang Y, et al., 2009. Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. Proc Natl Acad Sci USA, 106(6):1903-1908.

[32]Komatsu N, Okamoto K, Sawa S, et al., 2014. Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis. Nat Med, 20(1):62-68.

[33]Krishnamoorthy N, Khare A, Oriss TB, et al., 2012. Early infection with respiratory syncytial virus impairs regulatory T cell function and increases susceptibility to allergic asthma. Nat Med, 18(10):1525-1530.

[34]Lapierre P, Béland K, Yang R, et al., 2013. Adoptive transfer of ex vivo expanded regulatory T cells in an autoimmune hepatitis murine model restores peripheral tolerance. Hepatology, 57(1):217-227.

[35]Lewkowich IP, Herman NS, Schleifer KW, et al., 2005. CD4+CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function. J Exp Med, 202(11):1549-1561.

[36]Liang BT, Workman C, Lee J, et al., 2008. Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class II. J Immunol, 180(9):5916-5926.

[37]Lu YJ, Wang JR, Gu J, et al., 2014. Rapamycin regulates iTreg function through CD39 and Runx1 pathways. J Immunol Res, 2014:989434.

[38]Massoud AH, Charbonnier LM, Lopez D, et al., 2016. An asthma-associated IL4R variant exacerbates airway inflammation by promoting conversion of regulatory T cells to TH17-like cells. Nat Med, 22(9):1013-1022.

[39]Mathias CB, Hobson SA, Garcia-Lloret M, et al., 2011. IgE-mediated systemic anaphylaxis and impaired tolerance to food antigens in mice with enhanced IL-4 receptor signaling. J Allergy Clin Immunol, 127(3):795-805.e6.

[40]Melnik BC, John SM, Carrera-Bastos P, et al., 2016. Milk: a postnatal imprinting system stabilizing FoxP3 expression and regulatory T cell differentiation. Clin Transl Allergy, 6:18.

[41]Miyara M, Yoshioka Y, Kitoh A, et al., 2009. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity, 30(6):899-911.

[42]Nakamura K, Kitani A, Fuss I, et al., 2004. TGF-β1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice. J Immunol, 172(2):834-842.

[43]Nakao A, Miike S, Hatano M, et al., 2000. Blockade of transforming growth factor β/Smad signaling in T cells by overexpression of Smad7 enhances antigen-induced airway inflammation and airway reactivity. J Exp Med, 192(2):151-158.

[44]Niedbala W, Wei XQ, Cai BL, et al., 2007. IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells. Eur J Immunol, 37(11):3021-3029.

[45]Nieminen K, Laaksonen K, Savolainen J, 2009. Three-year follow-up study of allergen-induced in vitro cytokine and signalling lymphocytic activation molecule mRNA responses in peripheral blood mononuclear cells of allergic rhinitis patients undergoing specific immunotherapy. Int Arch Allergy Immunol, 150(4):370-376.

[46]Noval Rivas M, Burton OT, Wise P, et al., 2015. Regulatory T cell reprogramming toward a Th2-cell-like lineage impairs oral tolerance and promotes food allergy. Immunity, 42(3):512-523.

[47]Oh JW, Seroogy CM, Meyer EH, et al., 2002. CD4 T-helper cells engineered to produce IL-10 prevent allergen-induced airway hyperreactivity and inflammation. J Allergy Clin Immunol, 110(3):460-468.

[48]Ohnmacht C, Park JH, Cording S, et al., 2015. The microbiota regulates type 2 immunity through RORγt+ T cells. Science, 349(6251):989-993.

[49]Olson BM, Sullivan JA, Burlingham WJ, 2013. Interleukin 35: a key mediator of suppression and the propagation of infectious tolerance. Front Immunol, 4:315.

[50]Prinz I, Koenecke C, 2012. Therapeutic potential of induced and natural FoxP3+ regulatory T cells for the treatment of Graft-versus-host disease. Arch Immunol Ther Exp (Warsz), 60(3):183-190.

[51]Read S, Malmström V, Powrie F, 2000. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25+CD4+ regulatory cells that control intestinal inflammation. J Exp Med, 192(2):295-302.

[52]Reddel HK, Levy ML, 2015. The GINA asthma strategy report: what’s new for primary care? NPJ Prim Care Respir Med, 25:15050.

[53]Rosa-Rosa L, Zimmermann N, Bernstein JA, et al., 1999. The R576 IL-4 receptor α allele correlates with asthma severity. J Allergy Clin Immunol, 104(5):1008-1014.

[54]Round JL, Mazmanian SK, 2010. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci USA, 107(27):12204-12209.

[55]Round JL, Lee SM, Li J, et al., 2011. The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science, 332(6032):974-977.

[56]Rudensky AY, 2011. Regulatory T cells and Foxp3. Immunol Rev, 241(1):260-268.

[57]Sagoo P, Ali N, Garg G, et al., 2011. Human regulatory T cells with alloantigen specificity are more potent inhibitors of alloimmune skin graft damage than polyclonal regulatory T cells. Sci Transl Med, 3(83):83ra42.

[58]Sakaguchi S, Wing K, Onishi Y, et al., 2009. Regulatory T cells: how do they suppress immune responses? Int Immunol, 21(10):1105-1111.

[59]Sato H, Sasaki N, Minamitani K, et al., 2012. Higher dose of methimazole causes frequent adverse effects in the management of Graves’ disease in children and adolescents. J Pediatr Endocrinol Metab, 25(9-10):863-867.

[60]Scottà C, Esposito M, Fazekasova H, et al., 2013. Differential effects of rapamycin and retinoic acid on expansion, stability and suppressive qualities of human CD4+CD25+ FOXP3+ T regulatory cell subpopulations. Haematologica, 98(8):1291-1299.

[61]Sitkovsky M, Lukashev D, Deaglio S, et al., 2008. Adenosine A2A receptor antagonists: blockade of adenosinergic effects and T regulatory cells. Br J Pharmacol, 153(S1):S457-S464.

[62]Smith PM, Howitt MR, Panikov N, et al., 2013. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science, 341(6145):569-573.

[63]Stämpfli MR, Cwiartka M, Gajewska BU, et al., 1999. Interleukin-10 gene transfer to the airway regulates allergic mucosal sensitization in mice. Am J Respir Cell Mol Biol, 21(5):586-596.

[64]Stanilov NS, Miteva L, Cirovski G, et al., 2016. Increased transforming growth factor β and interleukin 10 transcripts in peripheral blood mononuclear cells of colorectal cancer patients. Contemp Oncol, 20(6):458-462.

[65]Stelmach I, Sobocińska A, Majak P, et al., 2012. Comparison of the long-term efficacy of 3- and 5-year house dust mite allergen immunotherapy. Ann Allergy Asthma Immunol, 109(4):274-278.

[66]Suárez-Fueyo A, Ramos T, Galán A, et al., 2014. Grass tablet sublingual immunotherapy downregulates the TH2 cytokine response followed by regulatory T-cell generation. J Allergy Clin Immunol, 133(1):130-138.e2.

[67]Swamy RS, Reshamwala N, Hunter T, et al., 2012. Epigenetic modifications and improved regulatory T-cell function in subjects undergoing dual sublingual immunotherapy. J Allergy Clin Immunol, 130(1):215-224.e7.

[68]Tachdjian R, Mathias C, Al Khatib S, et al., 2009. Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma. J Exp Med, 206(10):2191-2204.

[69]Tachdjian R, Al Khatib S, Schwinglshackl A, et al., 2010. In vivo regulation of the allergic response by the IL-4 receptor α chain immunoreceptor tyrosine-based inhibitory motif. J Allergy Clin Immunol, 125(5):1128-1136.e8.

[70]Thornton AM, Shevach EM, 1998. CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med, 188(2):287-296.

[71]Wang L, Fan J, Chen SQ, et al., 2013. Graft-versus-host disease is enhanced by selective CD73 blockade in mice. PLoS ONE, 8(3):e58397.

[72]Wills-Karp M, Santeliz J, Karp CL, 2001. The germless theory of allergic disease: revisiting the hygiene hypothesis. Nat Rev Immunol, 1(1):69-75.

[73]Won HY, Hwang ES, 2016. Transcriptional modulation of regulatory T cell development by novel regulators NR4As. Arch Pharm Res, 39(11):1530-1536.

[74]Xia MC, Viera-Hutchins L, Garcia-Lloret M, et al., 2015. Vehicular exhaust particles promote allergic airway inflammation through an aryl hydrocarbon receptor-notch signaling cascade. J Allergy Clin Immunol, 136(2):441-453.

[75]Yawn J, Lawrence LA, Carroll WW, et al., 2015. Vitamin D for the treatment of respiratory diseases: is it the end or just the beginning? J Steroid Biochem Mol Biol, 148:326-337.

[76]Zheng Y, Chaudhry A, Kas A, et al., 2009. Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control TH2 responses. Nature, 458(7236):351-356.

[77]Zhou XY, Bailey-Bucktrout S, Jeker LT, et al., 2009. Plasticity of CD4+FoxP3+ T cells. Curr Opin Immunol, 21(3):281-285.

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