调节性T细胞在特应性皮炎中的研究进展
Research Progress of Regulatory T Cells in Atopic Dermatitis
DOI: 10.12677/ACM.2022.124413, PDF,   
作者: 郝志玲, 柏冰雪*：哈尔滨医科大学附属第二医院，黑龙江 哈尔滨
关键词: 特应性皮炎；免疫反应；调节性T细胞；Atopic Dermatitis； Immune Response； Regulatory T Cells
摘要: 调节性T细胞是控制过敏反应不可或缺的一部分，在免疫抑制中起着关键作用。近年来研究发现，和许多炎症性疾病一样，调节性T细胞在特应性皮炎中也起着关键作用。文章综述了调节性T细胞的特性、功能、抑制机制研究进展以及在特应性皮炎中作用的研究进展，并揭示了目前直接或间接针对调节性T细胞的自身免疫性疾病的治疗策略，阐述了一种新的靶向调节性T细胞治疗方法，为今后特应性皮炎的治疗提供指导。
Abstract: Regulatory T cells are an indispensable part of controlling allergic reactions and play a key role in immunosuppression. In recent years, studies have found that, like many inflammatory diseases, regulatory T cells also play a key role in atopic dermatitis. This paper reviews the research progress on the characteristics, function and inhibitory mechanism of regulatory T cells and the role of regulatory T cells in atopic dermatitis, and reveals the current treatment strategies for auto-immune diseases directly or indirectly targeting regulatory T cells. This paper describes a new targeted regulatory T cell therapy to provide guidance for the treatment of atopic dermatitis in the future.
文章引用：郝志玲, 柏冰雪. 调节性T细胞在特应性皮炎中的研究进展[J]. 临床医学进展, 2022, 12(4): 2874-2880. https://doi.org/10.12677/ACM.2022.124413

参考文献

[1] 中国特应性皮炎诊疗指南(2020版) [J]. 中华皮肤科杂志, 2020, 53(2): 81-88.
[2] Grinberg-Bleyer, Y., Caron, R., Seeley, J.J, et al. (2018) The Alternative NF-kappaB Pathway in Regulatory T Cell Homeostasis and Suppressive Function. The Journal of Immunology, 200, 2362-2371. [Google Scholar] [CrossRef] [PubMed]
[3] Roesner, L.M., Floess, S., Witte, T., et al. (2015) Foxp3(+) Reg-ulatory T Cells Are Expanded in Severe Atopic Dermatitis Patients. Allergy, 70, 1656-1660. [Google Scholar] [CrossRef] [PubMed]
[4] Moosbrugger-Martinz, V., Tripp, C.H., Clausen, B.E, et al. (2016) Atopic Dermatitis Induces the Expansion of Thymus-Derived Regulatory T Cells Exhibiting a Th2-Like Phenotype in Mice. Journal of Cellular and Molecular Medicine, 20, 930-938. [Google Scholar] [CrossRef] [PubMed]
[5] Agrawal, R., Wisniewski, J.A. and Woodfolk, J.A. (2011) The Role of Regulatory T Cells in Atopic Dermatitis. Current Problems in Dermatology, 41, 112-124. [Google Scholar] [CrossRef] [PubMed]
[6] Keubler, L.M., Buettner, M., Hager, C., et al. (2015) A Multihit Model: Colitis Lessons from the Interleukin-10-Deficient Mouse. Inflammatory Bowel Diseases, 21, 1967-1975. [Google Scholar] [CrossRef] 
[7] Fyhrquist, N., Lehtimaki, S., Lahl, K., et al. (2012) Foxp3+ Cells Control Th2 Responses in a Murine Model of Atopic Dermatitis. Journal of Investigative Dermatology, 132, 1672-1680. [Google Scholar] [CrossRef] [PubMed]
[8] Nie, J., Li, Y.Y., Zheng, S.G., et al. (2015) FOXP3(+) Treg Cells and Gender Bias in Autoimmune Diseases. Frontiers in Immunology, 6, Article No. 493. [Google Scholar] [CrossRef] [PubMed]
[9] Noval Rivas, M. and Chatila, T.A. (2016) Regulatory T Cells in Allergic Diseases. The Journal of Allergy and Clinical Immunology, 138, 639-652. [Google Scholar] [CrossRef] [PubMed]
[10] Shin, J.U., Kim, S.H., Noh, J.Y., et al. (2018) Allergen-Specific Immunotherapy Induces Regulatory T Cells in an Atopic Dermatitis Mouse Model. Allergy, 73, 1801-1811. [Google Scholar] [CrossRef] [PubMed]
[11] Malhotra, N., Leyva-Castillo, J.M., Jadhav, U., et al. (2018) RORalpha-Expressing T Regulatory Cells Restrain Allergic Skin Inflammation. Science Immunology, 3, eaao6923. [Google Scholar] [CrossRef] [PubMed]
[12] Halabi-Tawil, M., Ruemmele, F.M., Fraitag, S., et al. (2009) Cutaneous Manifestations of Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked (IPEX) Syndrome. British Journal of Dermatology, 160, 645-651. [Google Scholar] [CrossRef] [PubMed]
[13] Gaspar, K., Barath, S., Nagy, G., et al. (2015) Regulatory T-Cell Subsets with Acquired Functional Impairment: Important Indicators of Disease Severity in Atopic Dermatitis. Acta Dermato-Venereologica, 95, 151-155. [Google Scholar] [CrossRef] [PubMed]
[14] Zhang, Y.Y., Wang, A.X., Xu, L., et al. (2016) Characteristics of Peripheral Blood CD4+CD25+ Regulatory T Cells and Related Cytokines in Severe Atopic Dermatitis. European Journal of Dermatology, 26, 240-246. [Google Scholar] [CrossRef] [PubMed]
[15] Hinz, D., Bauer, M., Roder, S., et al. (2012) Cord Blood Tregs with Stable FOXP3 Expression Are Influenced by Prenatal Environment and Associated with Atopic Dermatitis at the Age of One Year. Allergy, 67, 380-389. [Google Scholar] [CrossRef] [PubMed]
[16] Schaub, B., Liu, J., Hoppler, S., et al. (2008) Impairment of T-Regulatory Cells in Cord Blood of Atopic Mothers. The Journal of Allergy and Clinical Immunology, 121, 1491-1499, 1499.e1-13. [Google Scholar] [CrossRef] [PubMed]
[17] Kim, H.J., Kim, Y.J., Lee, S.H., et al. (2014) Effects of Lactobacillus rhamnosus on Allergic March Model by Suppressing Th2, Th17, and TSLP Responses via CD4(+)CD25(+)Foxp3(+) Tregs. Clinical Immunology, 153, 178-186. [Google Scholar] [CrossRef] [PubMed]
[18] Lin, Y.T., Wang, C.T., Chao, P.S., et al. (2011) Skin-Homing CD4+ Foxp3+ T Cells Exert Th2-Like Function after Staphylococcal Superantigen Stimulation in Atopic Dermatitis Patients. Clinical & Experimental Allergy, 41, 516-525. [Google Scholar] [CrossRef] [PubMed]
[19] Mittag, D., Scholzen, A., Varese, N., et al. (2010) The Effector T Cell Response to Ryegrass Pollen Is Counter Regulated by Simultaneous Induction of Regulatory T Cells. The Journal of Immunology, 184, 4708-4716. [Google Scholar] [CrossRef] [PubMed]
[20] Mobs, C., Slotosch, C., Loffler, H., et al. (2010) Birch Pollen Immunotherapy Leads to Differential Induction of Regulatory T Cells and Delayed Helper T Cell Immune Deviation. The Journal of Immunology, 184, 2194-2203. [Google Scholar] [CrossRef] [PubMed]
[21] Thunberg, S., Akdis, M., Akdis, C.A., et al. (2007) Immune Regulation by CD4+CD25+ T Cells and Interleukin-10 in Birch Pollen-Allergic Patients and Non-Allergic Controls. Clinical & Experimental Allergy, 37, 1127-1136. [Google Scholar] [CrossRef] [PubMed]
[22] Kuhn, C. and Weiner, H.L. (2016) Therapeutic Anti-CD3 Monoclonal Antibodies from Bench to Bedside. Immunotherapy, 8, 889-906. [Google Scholar] [CrossRef] [PubMed]
[23] Spence, A., Klementowicz, J.E., Bluestone, J.A., et al. (2015) Tar-geting Treg Signaling for the Treatment of Autoimmune Diseases. Current Opinion in Immunology, 37, 11-20. [Google Scholar] [CrossRef] [PubMed]
[24] Powell, J.D. and Delgoffe, G.M. (2010) The Mammalian Target of Rapamycin: Linking T Cell Differentiation, Function, and Metabolism. Immunity, 33, 301-311. [Google Scholar] [CrossRef] [PubMed]
[25] Charbonnier, L.M., Cui, Y., Stephen-Victor, E., et al. (2019) Functional Reprogramming of Regulatory T Cells in the Absence of Foxp3. Nature Immunology, 20, 1208-1219. [Google Scholar] [CrossRef] [PubMed]
[26] Son, S.E., Park, S.J., Koh, J.M., et al. (2020) Free Fatty Acid Receptor 4 (FFA4) Activation Ameliorates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis by Increasing Regu-latory T Cells in Mice. Acta Pharmacologica Sinica, 41, 1337-1347. [Google Scholar] [CrossRef] [PubMed]
[27] Nasri, H. and Rafieian-Kopaei, M. (2014) Metformin: Current Knowledge. Journal of Research in Medical Sciences, 19, 658-664.
[28] Fischer, K.E., Gelfond, J.A., Soto, V.Y., et al. (2015) Health Effects of Long-Term Rapamycin Treatment: The Impact on Mouse Health of Enteric Rapamycin Treatment from Four Months of Age throughout Life. PLoS ONE, 10, e0126644. [Google Scholar] [CrossRef] [PubMed]
[29] Danikowski, K.M., Jayaraman, S. and Prabhakar, B.S. (2017) Regulatory T Cells in Multiple Sclerosis and Myasthenia Gravis. Journal of Neuroinflammation, 14, Article No. 117. [Google Scholar] [CrossRef] [PubMed]
[30] Marek-Trzonkowska, N., Mysliwiec, M., Dobyszuk, A., et al. (2014) Therapy of Type 1 Diabetes with CD4(+)CD25(High)CD127-Regulatory T Cells Prolongs Survival of Pancreatic Islets-Results of One Year Follow-Up. Clinical Immunology, 153, 23-30. [Google Scholar] [CrossRef] [PubMed]
[31] Bluestone, J.A., Buckner, J.H., Fitch, M., et al. (2015) Type 1 Diabetes Immunotherapy Using Polyclonal Regulatory T Cells. Science Translational Medicine, 7, 315ra189. [Google Scholar] [CrossRef] [PubMed]
[32] Mathew, J.M., Lefever, A., et al. (2018) A Phase I Clinical Trial with ex Vivo Expanded Recipient Regulatory T Cells in Living Donor Kidney Transplants. Scientific Reports, 8, Article No. 7428. [Google Scholar] [CrossRef] [PubMed]
[33] Nikolouli, E., Hardtke-Wolenski, M., Hapke, M., et al. (2017) Alloantigen-Induced Regulatory T Cells Generated in Presence of Vitamin C Display Enhanced Stability of Foxp3 Ex-pression and Promote Skin Allograft Acceptance. Frontiers in Immunology, 8, Article No. 748. [Google Scholar] [CrossRef] [PubMed]
[34] Saadoun, D., et al. (2011) Regulatory T-Cell Responses to Low-Dose Interleukin-2 in HCV-Induced Vasculitis. The New England Journal of Medicine, 365, 2067-2077. [Google Scholar] [CrossRef] 
[35] Koreth, J., Matsuoka, K., Kim, H.T., et al. (2011) Interleukin-2 and Regulatory T Cells in Graft-Versus-Host Disease. New England Journal of Medicine, 365, 2055-2066. [Google Scholar] [CrossRef] 
[36] Brunstein, C.G., Miller, J.S., Mckenna, D.H., et al. (2016) Umbil-ical Cord Blood-Derived T Regulatory Cells to Prevent GVHD: Kinetics, Toxicity Profile, and Clinical Effect. Blood, 127, 1044-1051. [Google Scholar] [CrossRef] [PubMed]
[37] Rosenzwajg, M., Lorenzon, R., Cacoub, P., et al. (2019) Immunological and Clinical Effects of Low-Dose Interleukin-2 across 11 Autoimmune Diseases in a Single, Open Clinical Trial. Annals of the Rheumatic Diseases, 78, 209-217. [Google Scholar] [CrossRef] [PubMed]
[38] Castela, E., Le Duff, F., Butori, C., et al. (2014) Effects of Low-Dose Recombinant Interleukin 2 to Promote T-Regulatory Cells in Alopecia Areata. JAMA Dermatology, 150, 748-751. [Google Scholar] [CrossRef] [PubMed]
[39] Humrich, J.Y. and Riemekasten, G. (2016) Clinical Trials: The Rise of IL-2 Therapy—A Novel Biologic Treatment for SLE. Nature Reviews Rheumatology, 12, 695-696. [Google Scholar] [CrossRef] [PubMed]
[40] Rosenzwajg, M., Churlaud, G., Mallone, R., et al. (2015) Low-Dose Interleukin-2 Fosters a Dose-Dependent Regulatory T Cell Tuned Milieu in T1D Patients. Journal of Auto-immunity, 58, 48-58. [Google Scholar] [CrossRef] [PubMed]
[41] Hartemann, A., Bensimon, G., Payan, C.A., et al. (2013) Low-Dose Interleukin 2 in Patients with Type 1 Diabetes: A Phase 1/2 Randomised, Double-Blind, Placebo-Controlled Trial. The Lancet Diabetes & Endocrinology, 1, 295-305. [Google Scholar] [CrossRef] 

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