Regulatory T cell-based therapies for type 1 diabetes: a narrative review

Tsvetelina Velikova , Georgi V. Vasilev , Diya Linkwinstar , Elina Siliogka , Maria Kokudeva , Dimitrina Miteva , Georgi H. Vasilev , Milena Gulinac , Kiril Atliev , Russka Shumnalieva

Metabolism and Target Organ Damage ›› 2025, Vol. 5 ›› Issue (2) : 18

PDF
Metabolism and Target Organ Damage ›› 2025, Vol. 5 ›› Issue (2) :18 DOI: 10.20517/mtod.2024.52
Review

Regulatory T cell-based therapies for type 1 diabetes: a narrative review

Author information +
History +
PDF

Abstract

Type 1 diabetes (T1D) is an autoimmune disease caused by the destruction of pancreatic insulin-secreting beta cells, resulting in hyperglycemia and a lifelong need for exogenous insulin therapy. Regulatory T cells (Tregs) are essential for maintaining immune tolerance and preventing autoimmune reactions. It has been shown that dysfunctional Tregs participate in the pathophysiology of T1D. Therapeutic approaches designed to enhance Treg stability, survival, and function have progressively emerged as a promising treatment strategy for T1D. This narrative review explores the potential of Treg cell-based therapy as a therapeutic tool to alter the natural history of T1D. It discusses different pharmacological strategies to enhance Treg stability and function, as well as the latest advances in Treg cell-based therapies, including adoptive Treg cell therapy and genetic engineering of Tregs. It also outlines current challenges and future research directions for integrating Treg cell-based therapy into clinical practice, aiming to provide a comprehensive overview of its potential benefits and limitations as an innovative therapeutic intervention for T1D.

Keywords

Regulatory T cells / type 1 diabetes / immune regulation / autoimmune diseases / Treg cell-based therapy / pancreatic beta cells / immunotherapy / T1D management / immune tolerance / cell-based therapy

Cite this article

Download citation ▾
Tsvetelina Velikova, Georgi V. Vasilev, Diya Linkwinstar, Elina Siliogka, Maria Kokudeva, Dimitrina Miteva, Georgi H. Vasilev, Milena Gulinac, Kiril Atliev, Russka Shumnalieva. Regulatory T cell-based therapies for type 1 diabetes: a narrative review. Metabolism and Target Organ Damage, 2025, 5(2): 18 DOI:10.20517/mtod.2024.52

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Gillespie KM.Type 1 diabetes: pathogenesis and prevention.CMAJ2006;175:165-70 PMCID:PMC1489998

[2]

Norris JM,Stene LC.Type 1 diabetes-early life origins and changing epidemiology.Lancet Diabetes Endocrinol2020;8:226-38 PMCID:PMC7332108

[3]

Gregory GA, Robinson TIG, Linklater SE, et al; International Diabetes Federation Diabetes Atlas Type 1 Diabetes in Adults Special Interest Group. Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: a modelling study. Lancet Diabetes Endocrinol. 2022;10:741-60.

[4]

World Obesity Federation. World Obesity Atlas 2023. Available from: https://www.aafp.org/pubs/afp/issues/2018/0801/p154.html. [Last accessed on 26 Mar 2025].

[5]

Riddell MC.Exercise in adults with type 1 diabetes mellitus.Nat Rev Endocrinol2023;19:98-111

[6]

Holt RIG,Hess-Fischl A.The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).Diabetologia2021;64:2609-52 PMCID:PMC8481000

[7]

Lind M,Kosiborod M.Glycemic control and excess mortality in type 1 diabetes.N Engl J Med2014;371:1972-82

[8]

Hughes JW, Riddlesworth TD, DiMeglio LA, Miller KM, Rickels MR, McGill JB; T1D Exchange Clinic Network. Autoimmune diseases in children and adults with type 1 diabetes from the T1D exchange clinic registry. J Clin Endocrinol Metab. 2016;101:4931-7. PMCID:PMC7530541

[9]

Milluzzo A,Brozzetti A.Risk for coexistent autoimmune diseases in familial and sporadic type 1 diabetes is related to age at diabetes onset.Endocr Pract2021;27:110-7

[10]

Hughes JW,Salam M.Late-onset T1DM and older age predict risk of additional autoimmune disease.Diabetes Care2019;42:32-8 PMCID:PMC6300704

[11]

Diabetes Association Professional Practice Committee. 2. Diagnosis and classification of diabetes: standards of care in diabetes-2024.Diabetes Care2024;47:S20-42 PMCID:PMC10725812

[12]

Bluestone JA,Herold KC.Immunotherapy: building a bridge to a cure for type 1 diabetes.Science2021;373:510-6

[13]

Bluestone JA,Eisenbarth G.Genetics, pathogenesis and clinical interventions in type 1 diabetes.Nature2010;464:1293-300 PMCID:PMC4959889

[14]

Wagner DH Jr.Overlooked mechanisms in type 1 diabetes etiology: how unique costimulatory molecules contribute to diabetogenesis.Front Endocrinol2017;8:208 PMCID:PMC5572340

[15]

Goswami TK,Dhawan M.Regulatory T cells (Tregs) and their therapeutic potential against autoimmune disorders - advances and challenges.Hum Vaccin Immunother2022;18:2035117 PMCID:PMC9009914

[16]

Brusko TM,Clare-Salzler MJ,Atkinson MA.Functional defects and the influence of age on the frequency of CD4+ CD25+ T-cells in type 1 diabetes.Diabetes2005;54:1407-14

[17]

Burrack AL,Fife BT.T cell-mediated beta cell destruction: autoimmunity and alloimmunity in the context of type 1 diabetes.Front Endocrinol2017;8:343 PMCID:PMC5723426

[18]

Pinheiro MM,Garo ML.Prevention and treatment of type 1 diabetes: in search of the ideal combination therapy targeting multiple immunometabolic pathways.Metab Target Organ Damage2024;4:19

[19]

Bettini M.Function, failure, and the future potential of tregs in type 1 diabetes.Diabetes2021;70:1211-9 PMCID:PMC8275894

[20]

Billingham RE,Medawar PB.Actively acquired tolerance of foreign cells.Nature1953;172:603-6

[21]

Weigle W.Immunological tolerance. Progress in immunology. Elsevier; 1971. pp. 1467-70.

[22]

Sullivan JA,Olson BM,Burlingham WJ.Infectious tolerance as seen with 2020 vision: the role of IL-35 and extracellular vesicles.Front Immunol2020;11:1867 PMCID:PMC7480133

[23]

Hori S,Sakaguchi S.Control of regulatory T cell development by the transcription factor Foxp3.Science2003;299:1057-61

[24]

Zhao H,Kang Y.Tregs: where we are and what comes next?.Front Immunol2017;8:1578 PMCID:PMC5705554

[25]

Georgiev P,Chatila TA.Regulatory T cells: the many faces of Foxp3.J Clin Immunol2019;39:623-40 PMCID:PMC6754763

[26]

Baecher-Allan C,Hafler DA.Human CD4+CD25+ regulatory T cells.Semin Immunol2004;16:89-98

[27]

Thornton AM,Tran DQ.Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells.J Immunol2010;184:3433-41 PMCID:PMC3725574

[28]

Su H,Wang P,Ma Y.Human CD4+CD25highCD127low/neg regulatory T cells. In: Mitry RR, Hughes RD, Editors. Human cell culture protocols. Totowa: Humana Press; 2012. pp. 287-99.

[29]

Dai Z,Xie Q.Natural CD8+CD122+ T cells are more potent in suppression of allograft rejection than CD4+CD25+ regulatory T cells.Am J Transplant2014;14:39-48

[30]

Yadav M,Davini D.Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo.J Exp Med2012;209:1713-22, S1 PMCID:PMC3457729

[31]

Cai J,Zhang G.The role of PD-1/PD-L1 axis in Treg development and function: implications for cancer immunotherapy.Onco Targets Ther2019;12:8437-45 PMCID:PMC6800566

[32]

Huang CT,Flies D.Role of LAG-3 in regulatory T cells.Immunity2004;21:503-13

[33]

Schmitt EG.Generation and function of induced regulatory T cells.Front Immunol2013;4:152 PMCID:PMC3685796

[34]

Workman CJ,Collison LW,Vignali DA.The development and function of regulatory T cells.Cell Mol Life Sci2009;66:2603-22 PMCID:PMC2715449

[35]

Shevach EM.tTregs, pTregs, and iTregs: similarities and differences.Immunol Rev2014;259:88-102 PMCID:PMC3982187

[36]

Shevach EM,Davidson TS.The critical contribution of TGF-beta to the induction of Foxp3 expression and regulatory T cell function.Eur J Immunol2008;38:915-7 PMCID:PMC2662375

[37]

Schmidt A,Krammer PH.Molecular mechanisms of treg-mediated T cell suppression.Front Immunol2012;3:51 PMCID:PMC3341960

[38]

Atkinson MA,Michels AW.Type 1 diabetes.Lancet2014;383:69-82 PMCID:PMC4380133

[39]

Ikegami H,Babaya N.Genetics and pathogenesis of type 1 diabetes: prospects for prevention and intervention.J Diabetes Investig2011;2:415-20 PMCID:PMC4014898

[40]

Rewers M.Environmental risk factors for type 1 diabetes.Lancet2016;387:2340-8 PMCID:PMC5571740

[41]

Redondo MJ, Geyer S, Steck AK, et al; Type 1 Diabetes TrialNet Study Group. A type 1 diabetes genetic risk score predicts progression of islet autoimmunity and development of type 1 diabetes in individuals at risk. Diabetes Care. 2018;41:1887-94.Diabetes Care2018;41:1887-94 PMCID:PMC6105323

[42]

Klak M,Kowalska P.Type 1 diabetes: genes associated with disease development.Cent Eur J Immunol2020;45:439-53 PMCID:PMC7882399

[43]

Morran MP,Khadra A.Immunogenetics of type 1 diabetes mellitus.Mol Aspects Med2015;42:42-60 PMCID:PMC4548800

[44]

Lehuen A,Zaccone P.Immune cell crosstalk in type 1 diabetes.Nat Rev Immunol2010;10:501-13

[45]

Scherm MG,Serr I,Richardson SJ.Beta cell and immune cell interactions in autoimmune type 1 diabetes: how they meet and talk to each other.Mol Metab2022;64:101565 PMCID:PMC9418549

[46]

Roep BO.The role of T-cells in the pathogenesis of Type 1 diabetes: from cause to cure.Diabetologia2003;46:305-21

[47]

Ilonen J,Veijola R.The heterogeneous pathogenesis of type 1 diabetes mellitus.Nat Rev Endocrinol2019;15:635-50

[48]

Leete P,Krogvold L.Differential insulitic profiles determine the extent of β-cell destruction and the age at onset of type 1 diabetes.Diabetes2016;65:1362-9

[49]

Li Y,Chu CQ.Th17 cells in type 1 diabetes: role in the pathogenesis and regulation by gut microbiome.Mediators Inflamm2015;2015:638470 PMCID:PMC4710950

[50]

Walker LS.CD4 T cell differentiation in type 1 diabetes.Clin Exp Immunol2016;183:16-29 PMCID:PMC4687517

[51]

Smith MJ,Gottlieb PA.Endotypes in T1D: B lymphocytes and early onset.Curr Opin Endocrinol Diabetes Obes2020;27:225-30 PMCID:PMC8049183

[52]

Wong FS.B cells in autoimmune diabetes.Rev Diabet Stud2005;2:121-35 PMCID:PMC1783559

[53]

Zóka A,Somogyi A.Altered immune regulation in type 1 diabetes.Clin Dev Immunol2013;2013:254874 PMCID:PMC3763577

[54]

Okubo Y,Butterworth J,Faustman DL.Treg activation defect in type 1 diabetes: correction with TNFR2 agonism.Clin Transl Immunology2016;5:e56 PMCID:PMC4735064

[55]

Hull CM,Tree TIM.Regulatory T cell dysfunction in type 1 diabetes: what’s broken and how can we fix it?.Diabetologia2017;60:1839-50 PMCID:PMC6448885

[56]

Belle TL, Coppieters KT, von Herrath MG. Type 1 diabetes: etiology, immunology, and therapeutic strategies.Physiol Rev2011;91:79-118

[57]

Visperas A.Are regulatory T cells defective in type 1 diabetes and can we fix them?.J Immunol2016;197:3762-70 PMCID:PMC5119643

[58]

Greenbaum CJ,Krischer J.Strength in numbers: opportunities for enhancing the development of effective treatments for type 1 diabetes-the TrialNet experience.Diabetes2018;67:1216-25 PMCID:PMC6014559

[59]

Li Z,Tsun A.FOXP3+ regulatory T cells and their functional regulation.Cell Mol Immunol2015;12:558-65 PMCID:PMC4579651

[60]

Baecher-Allan CM.The purification and functional analysis of human CD4+CD25high regulatory T cells.Curr Protoc Immunol2006;Chapter 7:7.4B.1-12

[61]

Devaud C,Kershaw MH.Foxp3 expression in T regulatory cells and other cell lineages.Cancer Immunol Immunother2014;63:869-76 PMCID:PMC11028988

[62]

Caramalho Í,Foxall RB.Regulatory T-cell development in the human thymus.Front Immunol2015;6:395 PMCID:PMC4522873

[63]

Harris F,Tree T.IL-2-based approaches to Treg enhancement.Clin Exp Immunol2023;211:149-63 PMCID:PMC10019135

[64]

Busse D,Hobiger K.Competing feedback loops shape IL-2 signaling between helper and regulatory T lymphocytes in cellular microenvironments.Proc Natl Acad Sci U S A2010;107:3058-63 PMCID:PMC2840293

[65]

Park JH,Jeon B.Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome: a systematic review.Autoimmun Rev2020;19:102526

[66]

Gao X,Ding G.Complement C3 deficiency prevent against the onset of streptozotocin-induced autoimmune diabetes involving expansion of regulatory T cells.Clin Immunol2011;140:236-43

[67]

Mathisen AF,Unger L.Molecular profiling of NOD mouse islets reveals a novel regulator of insulitis onset.Sci Rep2024;14:14669 PMCID:PMC11199597

[68]

Grinberg-Bleyer Y,You S.IL-2 reverses established type 1 diabetes in NOD mice by a local effect on pancreatic regulatory T cells.J Exp Med2010;207:1871-8 PMCID:PMC2931175

[69]

D’Alise AM,Feuerer M.The defect in T-cell regulation in NOD mice is an effect on the T-cell effectors.Proc Natl Acad Sci U S A2008;105:19857-62 PMCID:PMC2604930

[70]

Zhao Y,Darflinger R,Holterman MJ.Human cord blood stem cell-modulated regulatory T lymphocytes reverse the autoimmune-caused type 1 diabetes in nonobese diabetic (NOD) mice.PLoS One2009;4:e4226 PMCID:PMC2627485

[71]

Tarbell KV,Zuo X.Dendritic cell-expanded, islet-specific CD4+ CD25+ CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice.J Exp Med2007;204:191-201 PMCID:PMC2118426

[72]

Tarbell KV,Olson K,Steinman RM.CD25+ CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes.J Exp Med2004;199:1467-77 PMCID:PMC2211787

[73]

Cheatem D,Gangi E,Prabhakar BS.Modulation of dendritic cells using granulocyte-macrophage colony-stimulating factor (GM-CSF) delays type 1 diabetes by enhancing CD4+CD25+ regulatory T cell function.Clin Immunol2009;131:260-70 PMCID:PMC2701651

[74]

Lindley S,Bishop A,Peakman M.Defective suppressor function in CD4+CD25+ T-cells from patients with type 1 diabetes.Diabetes2005;54:92-9

[75]

Haseda F,Murase-Mishiba Y,Hanafusa T.CD4+ CD45RA- FoxP3high activated regulatory T cells are functionally impaired and related to residual insulin-secreting capacity in patients with type 1 diabetes.Clin Exp Immunol2013;173:207-16 PMCID:PMC3722921

[76]

Glisic-Milosavljevic S,Koppen M.Dynamic changes in CD4+ CD25+high T cell apoptosis after the diagnosis of type 1 diabetes.Clin Exp Immunol2007;150:75-82 PMCID:PMC2219285

[77]

Glisic-Milosavljevic S,Jailwala P.At-risk and recent-onset type 1 diabetic subjects have increased apoptosis in the CD4+CD25+ T-cell fraction.PLoS One2007;2:e146 PMCID:PMC1764033

[78]

Long SA,Bollyky PL.Defects in IL-2R signaling contribute to diminished maintenance of FOXP3 expression in CD4+CD25+ regulatory T-cells of type 1 diabetic subjects.Diabetes2010;59:407-15 PMCID:PMC2809970

[79]

Garg G,Yang JH.Type 1 diabetes-associated IL2RA variation lowers IL-2 signaling and contributes to diminished CD4+CD25+ regulatory T cell function.J Immunol2012;188:4644-53 PMCID:PMC3378653

[80]

McClymont SA,Lee MR.Plasticity of human regulatory T cells in healthy subjects and patients with type 1 diabetes.J Immunol2011;186:3918-26 PMCID:PMC3091943

[81]

Marwaha AK,Panagiotopoulos C.Cutting edge: increased IL-17-secreting T cells in children with new-onset type 1 diabetes.J Immunol2010;185:3814-8

[82]

Huang Q.Regulatory T cell-based therapy in type 1 diabetes: latest breakthroughs and evidence.Int Immunopharmacol2024;140:112724

[83]

Ghobadinezhad F,Mozaffari F.The emerging role of regulatory cell-based therapy in autoimmune disease.Front Immunol2022;13:1075813 PMCID:PMC9795194

[84]

Longhi MS,Vergani D.Regulatory T cells in autoimmune hepatitis: an updated overview.J Autoimmun2021;119:102619 PMCID:PMC8044040

[85]

Oo YH,Cole R.Liver homing of clinical grade Tregs after therapeutic infusion in patients with autoimmune hepatitis.JHEP Rep2019;1:286-96 PMCID:PMC7001578

[86]

de Picciotto S,Hsiao CJ.Selective activation and expansion of regulatory T cells using lipid encapsulated mRNA encoding a long-acting IL-2 mutein.Nat Commun2022;13:3866 PMCID:PMC9256694

[87]

Strauss L,Knights A,Knuth A.Selective survival of naturally occurring human CD4+CD25+Foxp3+ regulatory T cells cultured with rapamycin.J Immunol2007;178:320-9

[88]

Baron KJ.Clinical manufacturing of regulatory T cell products for adoptive cell therapy and strategies to improve therapeutic efficacy.Organogenesis2023;19:2164159 PMCID:PMC9870008

[89]

Telford WG.Flow cytometry and cell sorting.Front Med2023;10:1287884 PMCID:PMC10703423

[90]

Trzonkowski P,Battaglia M.Hurdles in therapy with regulatory T cells.Sci Transl Med2015;7:304ps18

[91]

Duggleby R,Madrigal JA.Clinical grade regulatory CD4+ T cells (Tregs): moving toward cellular-based immunomodulatory therapies.Front Immunol2018;9:252 PMCID:PMC5816789

[92]

Fraser H,Grageda N.A rapamycin-based GMP-compatible process for the isolation and expansion of regulatory T cells for clinical trials.Mol Ther Methods Clin Dev2018;8:198-209 PMCID:PMC5850906

[93]

Janssens I.Regulating the regulators: is introduction of an antigen-specific approach in regulatory T cells the next step to treat autoimmunity?.Cell Immunol2020;358:104236

[94]

Amini L,Fritsche E,Kaiser D.Clinical adoptive regulatory T cell therapy: state of the art, challenges, and prospective.Front Cell Dev Biol2022;10:1081644 PMCID:PMC9924129

[95]

Bluestone JA,Fitch M.Type 1 diabetes immunotherapy using polyclonal regulatory T cells.Sci Transl Med2015;7:315ra189 PMCID:PMC4729454

[96]

Uenishi GI,Yam JY.GNTI-122: an autologous antigen-specific engineered Treg cell therapy for type 1 diabetes.JCI Insight2024;9:e171844 PMCID:PMC11063937

[97]

Liston A.Homeostatic control of regulatory T cell diversity.Nat Rev Immunol2014;14:154-65

[98]

Amini L,Schmueck-Henneresse M.Super-Treg: toward a new era of adoptive treg therapy enabled by genetic modifications.Front Immunol2020;11:611638 PMCID:PMC7945682

[99]

Cabrera SM,Mirmira RG.Targeting regulatory T cells in the treatment of type 1 diabetes mellitus.Curr Mol Med2012;12:1261-72 PMCID:PMC3709459

[100]

Ballou LM.Rapamycin and mTOR kinase inhibitors.J Chem Biol2008;1:27-36 PMCID:PMC2698317

[101]

Battaglia M,Migliavacca B,Kaupper T.Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients.J Immunol2006;177:8338-47

[102]

Monti P,Maffi P.Rapamycin monotherapy in patients with type 1 diabetes modifies CD4+CD25+FOXP3+ regulatory T-cells.Diabetes2008;57:2341-7 PMCID:PMC2518485

[103]

Herold KC,Auger JA.Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus.N Engl J Med2002;346:1692-8

[104]

Keymeulen B,Ziegler AG.Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes.N Engl J Med2005;352:2598-608

[105]

Herold KC, Bundy BN, Long SA, et al; Type 1 Diabetes TrialNet Study Group. An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes. N Engl J Med. 2019;381:603-13. PMCID:PMC6776880

[106]

Sims EK, Bundy BN, Stier K, et al; Type 1 Diabetes TrialNet Study Group. Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals. Sci Transl Med. 2021;13:eabc8980. PMCID:PMC8610022

[107]

Evans-Molina C.Teplizumab approval for type 1 diabetes in the USA.Lancet Diabetes Endocrinol2023;11:76-7

[108]

Kokori E,Ogieuhi IJ.Teplizumab’s immunomodulatory effects on pancreatic β-cell function in type 1 diabetes mellitus.Clin Diabetes Endocrinol2024;10:23 PMCID:PMC11316332

[109]

Sims EK, Besser REJ, Dayan C, et al; NIDDK Type 1 Diabetes TrialNet Study Group. Screening for type 1 diabetes in the general population: a status report and perspective. Diabetes. 2022;71:610-23. PMCID:PMC9114719

[110]

Mital S.Cost effectiveness of teplizumab for prevention of type 1 diabetes among different target patient groups.Pharmacoeconomics2020;38:1359-72

[111]

Fanaropoulou NM,Koufakis T.Teplizumab: promises and challenges of a recently approved monoclonal antibody for the prevention of type 1 diabetes or preservation of residual beta cell function.Expert Rev Clin Immunol2024;20:185-96

[112]

Ludvigsson J,Hjorth M.GAD treatment and insulin secretion in recent-onset type 1 diabetes.N Engl J Med2008;359:1909-20

[113]

Ludvigsson J.Autoantigen treatment in type 1 diabetes: unsolved questions on how to select autoantigen and administration route.Int J Mol Sci2020;21:1598 PMCID:PMC7084272

[114]

Hjorth M,Rydén A,Ludvigsson J.GAD-alum treatment induces GAD65-specific CD4+CD25highFOXP3+ cells in type 1 diabetic patients.Clin Immunol2011;138:117-26

[115]

Hodak E.Alefacept: a review of the literature and practical guidelines for management.Dermatol Ther2004;17:383-92

[116]

Krueger GG.Selective targeting of T cell subsets: focus on alefacept - a remittive therapy for psoriasis.Expert Opin Biol Ther2002;2:431-41

[117]

Chamian F,Lee E.Alefacept (anti-CD2) causes a selective reduction in circulating effector memory T cells (Tem) and relative preservation of central memory T cells (Tcm) in psoriasis.J Transl Med2007;5:27 PMCID:PMC1906741

[118]

Rigby MR,Pinckney A.Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients.J Clin Invest2015;125:3285-96 PMCID:PMC4623571

[119]

Yamanouchi J,Serra P.Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity.Nat Genet2007;39:329-37 PMCID:PMC2886969

[120]

Dendrou CA.The IL-2/CD25 pathway determines susceptibility to T1D in humans and NOD mice.J Clin Immunol2008;28:685-96

[121]

Rosenzwajg M,Lorenzon R.Low-dose IL-2 in children with recently diagnosed type 1 diabetes: a Phase I/II randomised, double-blind, placebo-controlled, dose-finding study.Diabetologia2020;63:1808-21

[122]

Gonçalves GAR.Gene therapy: advances, challenges and perspectives.Einstein2017;15:369-75 PMCID:PMC5823056

[123]

Chellappan DK,Teoh KX.Gene therapy and type 1 diabetes mellitus.Biomed Pharmacother2018;108:1188-200

[124]

Srinivasan M,Arzoun H.Gene therapy - can it cure type 1 diabetes?.Cureus2021;13:e20516 PMCID:PMC8723777

[125]

Lin Y.Antiaging gene Klotho attenuates pancreatic β-cell apoptosis in type 1 diabetes.Diabetes2015;64:4298-311 PMCID:PMC4657580

[126]

Xu A,Li T.Interleukin-10 gene transfer into insulin-producing β cells protects against diabetes in non-obese diabetic mice.Mol Med Rep2015;12:3881-9

[127]

Tuomela K.Genetic engineering of regulatory T cells for treatment of autoimmune disorders including type 1 diabetes.Diabetologia2024;67:611-22

[128]

Li D,Luo Y.Transplantation of Aire-overexpressing bone marrow-derived dendritic cells delays the onset of type 1 diabetes.Int Immunopharmacol2017;49:13-20

[129]

Johnson MC,Tisch R.Genetic vaccination for re-establishing T-cell tolerance in type 1 diabetes.Hum Vaccin2011;7:27-36 PMCID:PMC3062240

[130]

Shigihara T,Oikawa Y.CXCL10 DNA vaccination prevents spontaneous diabetes through enhanced beta cell proliferation in NOD mice.J Immunol2005;175:8401-8

[131]

Xia F,Du J,Liu Y.Reg3g overexpression promotes β cell regeneration and induces immune tolerance in nonobese-diabetic mouse model.J Leukoc Biol2016;99:1131-40

[132]

Skyler JS.Hope vs hype: where are we in type 1 diabetes?.Diabetologia2018;61:509-16

[133]

Michels AW.Immune intervention in type 1 diabetes.Semin Immunol2011;23:214-9 PMCID:PMC3177994

[134]

Schweiger D. Recent advances in immune-based therapies for type 1 diabetes.Horm Res Paediatr2023;96:631-45

[135]

Manirarora JN.Combination therapy using IL-2/IL-2 monoclonal antibody complexes, rapamycin, and islet autoantigen peptides increases regulatory T cell frequency and protects against spontaneous and induced type 1 diabetes in nonobese diabetic mice.J Immunol2015;195:5203-14

[136]

Kabakchieva P,Gerasoudis S.Islet transplantation-immunological challenges and current perspectives.World J Transplant2023;13:107-21 PMCID:PMC10303418

[137]

Wang Q,Liu L.Pancreatic islet transplantation: current advances and challenges.Front Immunol2024;15:1391504 PMCID:PMC11180903

[138]

Long SA, Rieck M, Sanda S, et al; Diabetes TrialNet and the Immune Tolerance Network. Rapamycin/IL-2 combination therapy in patients with type 1 diabetes augments Tregs yet transiently impairs β-cell function. Diabetes. 2012;61:2340-8. PMCID:PMC3425404

[139]

Tanemura M,Kawamoto K.Rapamycin induces autophagy in islets: relevance in islet transplantation.Transplant Proc2009;41:334-8

[140]

Caridade M,Ribeiro RM.Mechanisms underlying CD4+ Treg immune regulation in the adult: from experiments to models.Front Immunol2013;4:378 PMCID:PMC3831161

[141]

Raffin C,Bluestone JA.Treg cell-based therapies: challenges and perspectives.Nat Rev Immunol2020;20:158-72 PMCID:PMC7814338

[142]

MacDonald KN,Levings MK.Methods to manufacture regulatory T cells for cell therapy.Clin Exp Immunol2019;197:52-63 PMCID:PMC6591148

[143]

Gootjes C,Roep BO.Defining human regulatory T cells beyond FOXP3: the need to combine phenotype with function.Cells2024;13:941 PMCID:PMC11172350

[144]

Chae WJ.Therapeutic potential of gene-modified regulatory T cells: from bench to bedside.Front Immunol2018;9:303 PMCID:PMC5820299

[145]

Bayati F,Valadi M,Foma AM.The therapeutic potential of regulatory T cells: challenges and opportunities.Front Immunol2020;11:585819 PMCID:PMC7844143

[146]

Massoud AH,Lopez D,Phipatanakul W.An asthma-associated IL4R variant exacerbates airway inflammation by promoting conversion of regulatory T cells to TH17-like cells.Nat Med2016;22:1013-22 PMCID:PMC5014738

[147]

Hennessy C,Hester J.Barriers to Treg therapy in Europe: from production to regulation.Front Med2023;10:1090721 PMCID:PMC9892909

[148]

Chen X,Zhan Y.CRISPR-Cas9 applications in T cells and adoptive T cell therapies.Cell Mol Biol Lett2024;29:52 PMCID:PMC11010303

[149]

Haque M,Fino K.Stem cell-derived tissue-associated regulatory T cells ameliorate the development of autoimmunity.Sci Rep2016;6:20588 PMCID:PMC4742827

[150]

Luo Y,Wang B.Single-cell transcriptomic analysis reveals disparate effector differentiation pathways in human Treg compartment.Nat Commun2021;12:3913 PMCID:PMC8222404

[151]

McGovern JL,Stauss HJ.Engineering specificity and function of therapeutic regulatory T cells.Front Immunol2017;8:1517 PMCID:PMC5686054

[152]

Reddy NR,Xiao Y.Engineering synthetic suppressor T cells that execute locally targeted immunoprotective programs.Science2024;386:eadl4793 PMCID:PMC11831968

[153]

Mashayekhi K,Faubion WA Jr.Biomaterial-enhanced treg cell immunotherapy: a promising approach for transplant medicine and autoimmune disease treatment.Bioact Mater2024;37:269-98 PMCID:PMC11061617

[154]

Zieliński M,Iwaszkiewicz-Grześ D.Combined therapy with CD4+ CD25highCD127- T regulatory cells and anti-CD20 antibody in recent-onset type 1 diabetes is superior to monotherapy: randomized phase I/II trial.Diabetes Obes Metab2022;24:1534-43

[155]

Infante M,Fabbri A.The heterogeneity of type 1 diabetes: from immunopathology to immune intervention. Translational autoimmunity. Elsevier; 2022. pp. 83-104.

AI Summary AI Mindmap
PDF

802

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/