Cited by 195Diabetes and associated disordersT-cell and B-cell ImmunologyPancreatic function and diabetes

The DOI matches its Crossref record; 109 of the 109 references it cites were found in a registry or an index.

Regulatory T cell dysfunction in type 1 diabetes: what's broken and how can we fix it?

Open access

Hull, Caroline M., Peakman, Mark, Tree, Timothy I. M.·2017·Diabetologia

DOI 10.1007/s00125-017-4377-1PMC PMC6448885

Open this paper in CoChat — free account Open PDF

Abstract

Type 1 diabetes is an autoimmune disease characterised by the destruction of insulin producing beta cells in the pancreas. Whilst it remains unclear what the original triggering factors for this destruction are, observations from the natural history of human type 1 diabetes, including incidence rates in twins, suggest that the disease results from a combination of genetic and environmental factors. Whilst many different immune cells have been implicated, including members of the innate and adaptive immune systems, a view has emerged over the past 10 years that beta cell damage is mediated by the combined actions of CD4 + and CD8 + T cells with specificity for islet autoantigens. In health, these potentially pathogenic T cells are held in check by multiple regulatory mechanisms, known collectively as ‘immunological tolerance’. This raises the question as to whether type 1 diabetes develops, at least in part, as a result of a defect in one or more of these control mechanisms. Immunological tolerance includes both central mechanisms (purging of the T cell repertoire of high-affinity autoreactive T cells in the thymus) and peripheral mechanisms, a major component of which is the action of a specialised subpopulation of T cells, known as regulatory T cells (Tregs). In this review, we highlight the evidence suggesting that a reduction in the functional capacity of different Treg populations contributes to disease development in type 1 diabetes. We also address current controversies regarding the putative causes of this defect and discuss strategies to correct it as a means to reduce or prevent islet destruction in a clinical setting.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1007/s00125-017-4377-1

Cites

109 of 109 references verified0 citation errors · 0 not checkable

Statistics

Fig. 1 Alterations in Treg phenotype and function observed in type 1 diabetes. FOXP3+ Tregs from individuals with type 1 diabetes are less able to control the proliferation of and cytokine production by effector CD4+ T cells compared with those from individuals without diabetes. This defective regulation may be owing to two non-mutually exclusive factors: differences in the Teff population (shown in red boxes) and/or Treg intrinsic defects (shown in blue boxes) (where differences overlap, details are shown in red/blue boxes). Additionally, the frequency and function of induced Tregs (iTregs) may play a role in promoting imbalance of the immune system in type 1 diabetes (green boxes). In many cases, these immunophenotypes may be influenced by gene polymorphisms associated with type 1 diabetes susceptibility (shown in grey boxes). Potential avenues for strengthening immune regulation by Treg invigoration are indicated in beige boxes. Red circles, IFN-γ/IL-17; green circles, IL-10. The grey arrow represents how unstable expression profiles of FOXP3 by Tregs increases the production of proinflammatory cytokines, promoting the function and expansion of islet-destructive Teff cells. MHC-CII, HLA-DRB1/HLA-DQA1/HLA-DQB1; STAT, signal transducer and activator of transcription; Th, T helperCC BY · PubMed Central

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The Role of Tumoral FOXP3 on Cell Proliferation, Migration, and Invasion in Gastric Cancer
Zhang, L., Xu, J., Zhang, X., Zhang, Y., Wang, L., Huang, X., & Xu, Z. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479442 · Cited by 4,090
A CD4+T-cell subset inhibits antigen-specific T-cell responses and prevents colitis
Groux, H., O’Garra, A., Bigler, M., Rouleau, M., Antonenko, S. V., de Vries, J. E., & Roncarolo, M. G. (1997) · Nature · doi:10.1038/39614 · Cited by 3,588
Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse
Brunkow, M. E., Jeffery, E. W., Hjerrild, K. A., Paeper, B. W., Clark, L. B., Yasayko, S.-A., Wilkinson, J. E., Galas, D. J., Ziegler, S. F., & Ramsdell, F. (2001) · Nature Genetics · doi:10.1038/83784 · Cited by 2,628
Functional Delineation and Differentiation Dynamics of Human CD4+ T Cells Expressing the FoxP3 Transcription Factor
Miyara, M., Yoshioka, Y., Kitoh, A., Shima, T., Wing, K., Niwa, A., Parizot, C., Taflin, C., Heike, T., Valeyre, D., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.03.019 · Cited by 2,291
X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy
Wildin, R. S., Ramsdell, F., Peake, J., Faravelli, F., Casanova, J., Buist, N. R. M., Levy‐Lahad, E., Mazzella, M., Goulet, O., Perroni, L., et al. (2001) · Nature Genetics · doi:10.1038/83707 · Cited by 1,916
Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes
Finland, G. O. T. 1. D. I., Todd, J. A., the Wellcome Trust Case Control Consortium, Walker, N. M., Cooper, J. D., Smyth, D. J., Downes, K., Plagnol, V., Bailey, R., Nejentsev, S., et al. (2007) · Nature Genetics · doi:10.1038/ng2068 · Cited by 1,456
Epigenetic Control of the foxp3 Locus in Regulatory T Cells
Floess, S., Freyer, J., Siewert, C., Baron, U., Olek, S., Polansky, J. K., Schlawe, K., Chang, H., Bopp, T., Schmitt, E., et al. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050038 · Cited by 1,296
Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25– T cells
Walker, M., Kasprowicz, D. J., Gersuk, V. H., Bénard, A., Landeghen, M. V., Buckner, J. H., & Ziegler, S. F. (2003) · Journal of Clinical Investigation · doi:10.1172/jci19441 · Cited by 1,242
In Vitro–expanded Antigen-specific Regulatory T Cells Suppress Autoimmune Diabetes
Tang, Q., Henriksen, K., Bi, M., Finger, E. B., Szot, G. L., Ye, J., Masteller, E. L., McDevitt, H. O., Bonyhadi, M. L., & Bluestone, J. A. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040139 · Cited by 1,232
In Vitro Generation of Interleukin 10–producing Regulatory CD4+ T Cells Is Induced by Immunosuppressive Drugs and Inhibited by T Helper Type 1 (Th1)– and Th2-inducing Cytokines
Barrat, F. J., Cua, D. J., Boonstra, A., Richards, D. F., Crain, C., Savelkoul, H. F. J., Malefyt, R. D. W., Coffman, R. L., Hawrylowicz, C. M., & O’Garra, A. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20011629 · Cited by 1,161

Show all 109 references

Sorted by citations

Type 1 diabetes
DiMeglio, L. A., Evans-Molina, C., & Oram, R. A. (2018) · The Lancet · doi:10.1016/s0140-6736(18)31320-5 · Cited by 1,561
The heterogeneous pathogenesis of type 1 diabetes mellitus
Ilonen, J., Lempainen, J., & Veijola, R. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0254-y · Cited by 522
Introducing the Endotype Concept to Address the Challenge of Disease Heterogeneity in Type 1 Diabetes
Battaglia, M., Ahmed, S., Anderson, M. S., Atkinson, M. A., Becker, D., Bingley, P. J., Bosi, E., Brusko, T. M., DiMeglio, L. A., Evans-Molina, C., et al. (2020) · Diabetes Care · doi:10.2337/dc19-0880 · Cited by 351
Self-citation
Current understanding of CTLA-4: from mechanism to autoimmune diseases
Hossen, M. M., Ma, Y., Yin, Z., Xia, Y., Du, J., Huang, J. Y., Huang, J. J., Zou, L., Ye, Z., & Huang, Z. W. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1198365 · Cited by 268
Alterations in microbiota of patients with COVID-19: potential mechanisms and therapeutic interventions
Wang, B., Zhang, L., Wang, Y., Dai, T., Qin, Z., Zhou, F., & Zhang, L. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00986-0 · Cited by 187
A Systematic Review of Phytochemistry, Pharmacology and Pharmacokinetics on Astragali Radix: Implications for Astragali Radix as a Personalized Medicine
Guo, Z., Lou, Y., Kong, M., Luo, Q., Liu, Z., & Wu, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20061463 · Cited by 169
The diabetes pandemic and associated infections: suggestions for clinical microbiology
Toniolo, A., Cassani, G., Puggioni, A., Rossi, A., Colombo, A., Onodera, T., & Ferrannini, E. (2018) · Reviews in Medical Microbiology · doi:10.1097/mrm.0000000000000155 · Cited by 157
IL-2-based approaches to Treg enhancement
Harris, F., Berdugo, Y. A., & Tree, T. I. M. (2022) · Clinical & Experimental Immunology · doi:10.1093/cei/uxac105 · Cited by 145
Self-citation
Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis─A Potential Therapeutic Intervention to Improve Lung Health
Verma, A., Bhagchandani, T., Rai, A., Nikita, N., Sardarni, U. K., Bhavesh, N. S., Gulati, S., Malik, R., & Tandon, R. (2024) · ACS Omega · doi:10.1021/acsomega.3c05846 · Cited by 127
Regulatory T Cells in Systemic Sclerosis
Frantz, C., Auffray, C., Avouac, J., & Allanore, Y. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02356 · Cited by 110
Mechanisms of human FoxP3+ Treg cell development and function in health and disease
Attias, M., Al-Aubodah, T.-A., & Piccirillo, C. A. (2019) · Clinical & Experimental Immunology · doi:10.1111/cei.13290 · Cited by 106
Emerging Therapeutics for Immune Tolerance: Tolerogenic Vaccines, T cell Therapy, and IL-2 Therapy
Moorman, C. D., Sohn, S. J., & Phee, H. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.657768 · Cited by 104
Pancreatic islet-specific engineered T regs exhibit robust antigen-specific and bystander immune suppression in type 1 diabetes models
Yang, S. J., Singh, A. K., Drow, T., Tappen, T., Honaker, Y., Barahmand-pour-Whitman, F., Linsley, P. S., Cerosaletti, K. M., Mauk, K. E., Xiang, Y., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abn1716 · Cited by 88
Function, Failure, and the Future Potential of Tregs in Type 1 Diabetes
Bettini, M., & Bettini, M. L. (2021) · Diabetes · doi:10.2337/dbi18-0058 · Cited by 89
A phase 2 randomized trial with autologous polyclonal expanded regulatory T cells in children with new-onset type 1 diabetes
Bender, C., WIEDEMAN, A. E., Hu, A. K., Ylescupidez, A., Sietsema, W. K., Herold, K. C., Griffin, K., Gitelman, S. E., Long, S. A., on behalf of the T-Rex Study Group†, et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adn2404 · Cited by 86
Immunological biomarkers for the development and progression of type 1 diabetes
Mathieu, C., Lahesmaa, R., Bonifacio, E. E., Achenbach, P., & Tree, T. I. M. (2018) · Diabetologia · doi:10.1007/s00125-018-4726-8 · Cited by 82
Self-citation
Why Is COVID-19 More Severe in Patients With Diabetes? The Role of Angiotensin-Converting Enzyme 2, Endothelial Dysfunction and the Immunoinflammatory System
Roberts, J., Pritchard, A. L., Treweeke, A. T., Rossi, A. G., Brace, N., Cahill, P. A., MacRury, S. M., Wei, J., & Megson, I. L. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.629933 · Cited by 68
Exercise and Type 1 Diabetes
Lu, X., & Zhao, C. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-981-15-1792-1_7 · Cited by 77
Advances in Chemical Composition, Extraction Techniques, Analytical Methods, and Biological Activity of Astragali Radix
Chang, X., Chen, X., Guo, Y., Gong, P., Pei, S., Wang, D., Wang, P., Wang, M., & Chen, F. (2022) · Molecules · doi:10.3390/molecules27031058 · Cited by 64
The β Cell in Diabetes: Integrating Biomarkers With Functional Measures
Kahn, S. E., Chen, Y., Esser, N., Taylor, A. J., van Raalte, D. H., Zraika, S., & Verchere, C. B. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnab021 · Cited by 75
Adult-onset autoimmune diabetes
Buzzetti, R., Maddaloni, E., Gaglia, J. L., Leslie, R. D., Wong, F. S., & Boehm, B. O. (2022) · Nature Reviews Disease Primers · doi:10.1038/s41572-022-00390-6 · Cited by 70
Defining the Threshold IL-2 Signal Required for Induction of Selective Treg Cell Responses Using Engineered IL-2 Muteins
Ghelani, A. P., Bates, D. L., Conner, K. P., Wu, M.-Z., Lu, J., Hu, Y.-L., Li, C.-M., Chaudhry, A., & Sohn, S. J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01106 · Cited by 58
Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes
Kong, B. S., Min, S. H., Lee, C. D., & Cho, Y. M. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109447 · Cited by 69
Targeting the receptor for advanced glycation end products (RAGE) in type 1 diabetes
Bagge, S. L., Fotheringham, A. K., Leung, S. S., & Forbes, J. M. (2020) · Medicinal Research Reviews · doi:10.1002/med.21654 · Cited by 54
Presumption of guilt for T cells in type 1 diabetes: lead culprits or partners in crime depending on age of onset?
Carré, A., Richardson, S. J., Larger, É., & Mallone, R. (2020) · Diabetologia · doi:10.1007/s00125-020-05298-y · Cited by 53
Innate inflammation drives NK cell activation to impair Treg activity
Dean, J. W., Peters, L. D., Fuhrman, C. A., Seay, H. R., Posgai, A. L., Stimpson, S. E., Brusko, M., Perry, D. J., Yeh, W.-I., Newby, B. N., et al. (2020) · Journal of Autoimmunity · doi:10.1016/j.jaut.2020.102417 · Cited by 50
Dipeptidyl peptidase-4(DPP-4) inhibitors: promising new agents for autoimmune diabetes
Wang, X., Zheng, P., Huang, G., Yang, L., & Zhou, Z. (2018) · Clinical and Experimental Medicine · doi:10.1007/s10238-018-0519-0 · Cited by 48
Tolerizing Strategies for the Treatment of Autoimmune Diseases: From ex vivo to in vivo Strategies
Cauwels, A., & Tavernier, J. H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00674 · Cited by 50
Advanced Glycation End Products and Inflammation in Type 1 Diabetes Development
Du, C., Whiddett, R. O., Buckle, I., Chen, C., Forbes, J. M., & Fotheringham, A. K. (2022) · Cells · doi:10.3390/cells11213503 · Cited by 49
Single-cell insights into immune dysregulation in rheumatoid arthritis flare versus drug-free remission
Baker, K. F., McDonald, D., Hulme, G., Hussain, R., Coxhead, J., Swan, D. J., Schulz, A. R., Mei, H. E., MacDonald, L., Pratt, A. G., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45213-2 · Cited by 48
Treg gene signatures predict and measure type 1 diabetes trajectory
Pesenacker, A. M., Chen, V., Gillies, J. K., Speake, C., Marwaha, A., Sun, A. C., Chow, S., Tan, R., Elliott, T. G., Dutz, J. P., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.123879 · Cited by 42
Modeling human T1D-associated autoimmune processes
Maharlooei, M. K., Madley, R., Borsotti, C., Ferreira, L. M. R., Sharp, R. C., Brehm, M. A., Greiner, D. L., Parent, A. V., Anderson, M. S., Sykes, M., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101417 · Cited by 42
Engineered Treg cells: The heir to the throne of immunotherapy
Stucchi, A., Maspes, F., Montee-Rodrigues, E., & Fousteri, G. (2023) · Journal of Autoimmunity · doi:10.1016/j.jaut.2022.102986 · Cited by 43
Role of Polyamines and Hypusine in β Cells and Diabetes Pathogenesis
Kulkarni, A., Anderson, C. M., Mirmira, R. G., & Tersey, S. A. (2022) · Metabolites · doi:10.3390/metabo12040344 · Cited by 40
Chimeric Antigen Receptor (CAR)-Based Cell Therapy for Type 1 Diabetes Mellitus (T1DM); Current Progress and Future Approaches
Mohammadi, V., Maleki, A. J., Nazari, M., Siahmansouri, A., Moradi, A., Elahi, R., & Esmaeilzadeh, A. (2023) · Stem Cell Reviews and Reports · doi:10.1007/s12015-023-10668-1 · Cited by 38
Type 1 diabetes: A new vision of the disease based on endotypes
Weston, C. S., Boehm, B. O., & Pozzilli, P. (2024) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3770 · Cited by 40
Immunomodulatory Properties of Natural Extracts and Compounds Derived from Bidens pilosa L.: Literature Review
Mesa, X. M. R., Bolaños, L. A. C., Mejía, A., Pombo, L. M., Costa, G. M., & González, S. P. S. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15051491 · Cited by 42
Progress in Translational Regulatory T Cell Therapies for Type 1 Diabetes and Islet Transplantation
Marfil‐Garza, B. A., Hefler, J., de León, M. B., Pawlick, R. L., Dadheech, N., & Shapiro, A. M. J. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa028 · Cited by 34
The Role of T Cell Receptor Signaling in the Development of Type 1 Diabetes
Clark, M., Kroger, C. J., Qi, K., & Tisch, R. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.615371 · Cited by 37
Therapies to Suppress β Cell Autoimmunity in Type 1 Diabetes
Kroger, C. J., Clark, M., Qi, K., & Tisch, R. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01891 · Cited by 35
Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity
Jiang, Z., Zhu, H., Wang, P., Que, W., Zhong, L., Li, X., & Du, F. (2022) · MedComm · doi:10.1002/mco2.137 · Cited by 35
Translating Mechanism of Regulatory Action of Tolerogenic Dendritic Cells to Monitoring Endpoints in Clinical Trials
Suwandi, J. S., Nikolić, T., & Roep, B. O. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01598 · Cited by 32
Slow progressors to type 1 diabetes lose islet autoantibodies over time, have few islet antigen-specific CD8+ T cells and exhibit a distinct CD95hi B cell phenotype
Hanna, S. J., Powell, W. E., Long, A. E., Robinson, E., Davies, J. E., Megson, C., Howell, A., Jones, T. J., Ladell, K., Price, D. A., et al. (2020) · Diabetologia · doi:10.1007/s00125-020-05114-7 · Cited by 32
Innate Viral Sensor MDA5 and Coxsackievirus Interplay in Type 1 Diabetes Development
Blum, S. I., & Tse, H. M. (2020) · Microorganisms · doi:10.3390/microorganisms8070993 · Cited by 31
Tregs and Mixed Chimerism as Approaches for Tolerance Induction in Islet Transplantation
Pathak, S., & Meyer, E. H. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.612737 · Cited by 32
Extracellular Vesicle Therapy for Type 1 Diabetes
Soltani, S., Mansouri, K., Aleagha, M. S. E., Moasefi, N., Yavari, N., Shakouri, S. K., Notararigo, S., Shojaeian, A., Pociot, F., & Yarani, R. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.865782 · Cited by 33
Islet Transplantation: Current Limitations and Challenges for Successful Outcomes
Langlois, A., Pinget, M., Kessler, L., & Bouzakri, K. (2024) · Cells · doi:10.3390/cells13211783 · Cited by 42
PPARs and the Development of Type 1 Diabetes
Holm, L. J., Mønsted, M. Ø., Haupt‐Jorgensen, M., & Buschard, K. (2020) · PPAR Research · doi:10.1155/2020/6198628 · Cited by 34
MAIT cell alterations in adults with recent-onset and long-term type 1 diabetes
Nel, I., Beaudoin, L., Gouda, Z., Rousseau, C., Soulard, P., Rouland, M., Bertrand, L., Boîtard, C., Larger, É., & Lehuen, A. (2021) · Diabetologia · doi:10.1007/s00125-021-05527-y · Cited by 30
Dipeptidyl peptidase-4 inhibitors (DPP-4i) combined with vitamin D3: An exploration to treat new-onset type 1 diabetes mellitus and latent autoimmune diabetes in adults in the future
Pinheiro, M. M., Pinheiro, F. M. M., & Trabachin, M. L. (2018) · International Immunopharmacology · doi:10.1016/j.intimp.2018.02.003 · Cited by 29
Targeting Glycoproteins as a therapeutic strategy for diabetes mellitus and its complications
Naseri, R., Navabi, S. J., Samimi, Z., Mishra, A. P., Nigam, M., Chandra, H., Olatunde, A., Tijjani, H., Morais‐Urano, R. P., & Farzaei, M. H. (2020) · DARU Journal of Pharmaceutical Sciences · doi:10.1007/s40199-020-00327-y · Cited by 31
Approaches in Immunotherapy, Regenerative Medicine, and Bioengineering for Type 1 Diabetes
Kopan, C., Tucker, T. R., Alexander, M., Mohammadi, M. R., Pone, E. J., & Lakey, J. R. T. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01354 · Cited by 28
Indirubin modulates CD4+ T‐cell homeostasis via PD1/PTEN/AKT signalling pathway in immune thrombocytopenia
Zhao, Y., Han, P., Liu, L., Wang, X., Xu, P., Wang, H., Yu, T., Sun, Y., Li, L., Sun, T., et al. (2019) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14089 · Cited by 28
Type 1 diabetes mellitus prevention: present and future
Henriques, F. L., Buckle, I., & Forbes, J. M. (2025) · Nature Reviews Endocrinology · doi:10.1038/s41574-025-01128-6 · Cited by 32
Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD): a phase 2, multicentre, double-blind, randomized, placebo-controlled trial
Marcovecchio, M. L., Wicker, L. S., Dunger, D. B., Dutton, S., Kopijasz, S., Scudder, C. L., Todd, J. A., & Johnson, P. R. V. (2020) · Wellcome Open Research · doi:10.12688/wellcomeopenres.15697.1 · Cited by 26
CD226 Attenuates Treg Proliferation via Akt and Erk Signaling in an EAE Model
Wang, N., Yi, H., Fang, L., Jin, J., Ma, Q., Shen, Y., Li, J., Liang, S., Xiong, J., Li, Z., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01883 · Cited by 28
Modulation of Intestinal ILC3 for the Treatment of Type 1 Diabetes
Stojanović, I., Saksida, T., Miljković, D. M., & Pejnovic, N. N. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.653560 · Cited by 30
Autologous regulatory T cells in clinical intraportal allogenic pancreatic islet transplantation
Bergström, M., Yao, M. H., Müller, M., Korsgren, O., von Zur‐Mühlen, B., & Lundgren, T. (2021) · Transplant International · doi:10.1111/tri.14163 · Cited by 29
Potential Therapeutic Application of Regulatory T Cells in Diabetes Mellitus Type 1
Beń‐Skowronek, I., Sieniawska, J., Pach, E., Wrobel, W., Skowronek, A., Tomczyk, Z., & Rosolowska, I. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010390 · Cited by 27
Human CD4+CD25+CD226- Tregs Demonstrate Increased Purity, Lineage Stability, and Suppressive Capacity Versus CD4+CD25+CD127lo/- Tregs for Adoptive Cell Therapy
Brown, M. E., Peters, L. D., Hanbali, S., Arnoletti, J. M., Sachs, L. K., Nguyen, K. Q., Carpenter, E. B., Seay, H. R., Fuhrman, C. A., Posgai, A. L., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.873560 · Cited by 24
MicroRNAs: markers of β-cell stress and autoimmunity
Dotta, F., Ventriglia, G., Snowhite, I. V., & Pugliese, A. (2018) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000420 · Cited by 27
Virus as the cause of type 1 diabetes
Dahl‐Jørgensen, K. (2024) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2024.06.011 · Cited by 29
Negative regulation of FOXP3 expression by c-Rel O-GlcNAcylation
de Jesus, T. J., Tomalka, J. A., Centore, J. T., Rodriguez, F. D. S., Agarwal, R. A., Liu, A. R., Kern, T. S., & Ramakrishnan, P. (2021) · Glycobiology · doi:10.1093/glycob/cwab001 · Cited by 27
Gut microbiome in type 1 diabetes: the immunological perspective
Rampanelli, E., & Nieuwdorp, M. (2022) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2023.2150612 · Cited by 29
Recent advancements on novel approaches of insulin delivery
Karmakar, S., Bhowmik, M., Laha, B., & Manna, S. (2023) · Medicine in Novel Technology and Devices · doi:10.1016/j.medntd.2023.100253 · Cited by 24
The Multifactorial Progression from the Islet Autoimmunity to Type 1 Diabetes in Children
Bauer, W., Gyenesei, A., & Kretowski, A. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147493 · Cited by 25
Targeting IL-12 family cytokines: A potential strategy for type 1 and type 2 diabetes mellitus
Luo, J., Ning, T., Li, X., Jiang, T., Tan, S., & Ma, D. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115958 · Cited by 21
Long, Noncoding RNA SRA Induces Apoptosis of β-Cells by Promoting the IRAK1/LDHA/Lactate Pathway
Huang, Y., Chiang, S., Lin, Y., Liu, S., Li, Y.-H., Liao, Y.-C., Lee, M.-R., Su, P., Tsai, F., Hung, H., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041720 · Cited by 19
Oral delivery of single-chain insulin (SCI-59) analog by bacterium-like particles (BLPs) induces oral tolerance and prevents autoimmune diabetes in NOD mice
Mao, R., Chen, Y., Wu, Q., Zhang, T., Diao, E., Wu, D., Wang, M., Liu, Y., Lu, L., Chang, X., et al. (2019) · Immunology Letters · doi:10.1016/j.imlet.2019.08.008 · Cited by 19
Oestrogen receptor α in T cells controls the T cell immune profile and glucose metabolism in mouse models of gestational diabetes mellitus
Tanaka, T., Wada, T., Uno, K., Ogihara, S., Ie, H., Okekawa, A., Ishikawa, A., Ito, T., Miyazawa, Y., Sameshima, A., et al. (2021) · Diabetologia · doi:10.1007/s00125-021-05447-x · Cited by 20
Auto-immunity and the gut microbiome in type 1 diabetes: Lessons from rodent and human studies
Snethlage, C. M. F., Nieuwdorp, M., van Raalte, D. H., Rampanelli, E., Verchere, C. B., & Hanssen, N. M. J. (2021) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2021.101544 · Cited by 18
Abnormal T-Cell Development in the Thymus of Non-obese Diabetic Mice: Possible Relationship With the Pathogenesis of Type 1 Autoimmune Diabetes
Mendes-da-Cruz, D., Lemos, J., Passos, G., & Savino, W. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00381 · Cited by 16
Interleukin-33 prevents the development of autoimmune diabetes in NOD mice
Lü, J., Liang, Y., Zhao, J., Meng, H., & Zhang, X. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.02.018 · Cited by 19
Phenotypic alterations in pancreatic lymph node stromal cells from human donors with type 1 diabetes and NOD mice
Postigo, J., Färber, D. L., & Creusot, R. J. (2019) · Diabetologia · doi:10.1007/s00125-019-04984-w · Cited by 17
Phenotypic Analysis of Human Lymph Nodes in Subjects With New-Onset Type 1 Diabetes and Healthy Individuals by Flow Cytometry
Yang, J. H. M., Khatri, L., Mickunas, M., Williams, E., Tatović, D., Ali, M. A., Young, P., Moyle, P., Sahni, V., Wang, R., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02547 · Cited by 18
Self-citation
Abnormal T Cell Frequencies, Including Cytomegalovirus-Associated Expansions, Distinguish Seroconverted Subjects at Risk for Type 1 Diabetes
Harms, R. Z., Lorenzo-Arteaga, K. M., Ostlund, K. R., Smith, V. B., Smith, L. M., Gottlieb, P. A., & Sarvetnick, N. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02332 · Cited by 17
Hematopoietic stem cell transplantation recovers insulin deficiency in type 1 diabetes mellitus associated with IPEX syndrome
Yamauchi, T., Takasawa, K., Kamiya, T., Kirino, S., Gau, M., Inoue, K., Hoshino, A., Kashimada, K., Kanegane, H., & Morio, T. (2019) · Pediatric Diabetes · doi:10.1111/pedi.12895 · Cited by 17
Candidate Biomarkers for the Prediction and Monitoring of Partial Remission in Pediatric Type 1 Diabetes
Gómez-Muñoz, L., Perna‐Barrull, D., Caroz-Armayones, J. M., Murillo, M., Rodríguez-Fernández, S., Valls, A., Vázquez, F., Pérez, J., Corripio, R., Castaño, L. A., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.825426 · Cited by 17
Targeting regulatory T cell metabolism in disease: Novel therapeutic opportunities
Halvorson, T., Tuomela, K., & Levings, M. K. (2023) · European Journal of Immunology · doi:10.1002/eji.202250002 · Cited by 18
Faecal microbiota transplantation in endocrine diseases and obesity
Snethlage, C. M. F., Nieuwdorp, M., & Hanssen, N. M. J. (2020) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2020.101483 · Cited by 15
Transient Depletion of Foxp3+ Regulatory T Cells Selectively Promotes Aggressive β Cell Autoimmunity in Genetically Susceptible DEREG Mice
Watts, D., Janßen, M., Jaykar, M. T., Palmucci, F., Weigelt, M., Petzold, C., Hommel, A., Sparwasser, T. D., Bonifacio, E. E., & Kretschmer, K. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.720133 · Cited by 15
Self-Antigens Targeted by Regulatory T Cells in Type 1 Diabetes
Mitchell, A. M., & Michels, A. W. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063155 · Cited by 15
Engineering human stellate cells for beta cell replacement therapy promotes in vivo recruitment of regulatory T cells
Oran, D. C., Lokumcu, T., Inceoglu, Y., Akolpoglu, M. B., Albayrak, Ö., Bal, T., Kurtoğlu, M., Erkan, M., Can, F., Onder, T. B., et al. (2019) · Materials Today Bio · doi:10.1016/j.mtbio.2019.100006 · Cited by 15
Tetrahedral Framework Nucleic Acids Reverse New-Onset Type 1 Diabetes
Gao, S., Zhou, M., Li, Y., Xiao, D., Wang, Y., Yao, Y., Gao, Y., Cai, X., & Lin, Y. (2021) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.1c16151 · Cited by 14
Clinical Incidence and Characteristics of Newly Diagnosed Type 1 Diabetes in Chinese Children and Adolescents: A Nationwide Registry Study of 34 Medical Centers
Li, G., Huang, K., Dong, G., Zhang, J., Gong, C., Luo, F., Luo, X., Wang, C., Zhu, M., Li, P., et al. (2022) · Frontiers in Pediatrics · doi:10.3389/fped.2022.888370 · Cited by 19
Human umbilical cord mesenchymal stem cell-derived TGFBI attenuates streptozotocin-induced type 1 diabetes mellitus by inhibiting T-cell proliferation
Wu, C., Liu, W., Liu, Y., Xu, T., Li, M., Li, X., Wang, Y., Meng, G., Li, L., Zheng, R., et al. (2023) · Human Cell · doi:10.1007/s13577-023-00868-9 · Cited by 14
The role and mechanism of mesenchymal stem cells in immunomodulation of type 1 diabetes mellitus and its complications: recent research progress and challenges: a review
Wang, C., Wu, Y., & Jiang, J. (2025) · Stem Cell Research & Therapy · doi:10.1186/s13287-025-04431-1 · Cited by 17
Redox Regulation of Tolerogenic Dendritic Cells and Regulatory T Cells in the Pathogenesis and Therapy of Autoimmunity
Saksida, T., Jevtić, B., Djedović, N., Miljković, D. M., & Stojanović, I. (2020) · Antioxidants and Redox Signaling · doi:10.1089/ars.2019.7999 · Cited by 14
Distinct cellular immune responses in children en route to type 1 diabetes with different first-appearing autoantibodies
Starskaia, I., Valta, M., Pietilä, S., Suomi, T., Pahkuri, S., Ullah, U., Rasool, O., Rydgren, E., Hyöty, H., Knip, M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-47918-w · Cited by 16
CD39 delineates chimeric antigen receptor regulatory T cell subsets with distinct cytotoxic & regulatory functions against human islets
Wu, X., Chen, P.-I., Whitener, R. L., MacDougall, M. S., Coykendall, V. M. N., Yan, H., Kim, Y. B., Harper, W., Pathak, S., Iliopoulou, B. P., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1415102 · Cited by 15
Nanotechnology in Immunotherapy for Type 1 Diabetes: Promising Innovations and Future Advances
Nigam, S., Bishop, J. O., Hayat, H., Quadri, T., Hayat, H., & Wang, P. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14030644 · Cited by 13
Diabetes, COVID‐19, and questions unsolved
D'souza, F., Buzzetti, R., & Pozzilli, P. (2023) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3666 · Cited by 13
Tipping the balance in autoimmunity: are regulatory t cells the cause, the cure, or both?
Hardtke‐Wolenski, M., & Landwehr-Kenzel, S. (2024) · Molecular and Cellular Pediatrics · doi:10.1186/s40348-024-00176-8 · Cited by 17
Regulatory CD4+ T cells redirected against pathogenic CD8+ T cells protect NOD mice from development of autoimmune diabetes
Kakabadse, D., Chen, D., Fishman, S., Weinstein-Marom, H., Davies, J. E., Li, W., Gross, G., & Wong, F. S. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1463971 · Cited by 12
Novel antimicrobial strategies for diabetic foot infections: addressing challenges and resistance
Alenazi, F., & Khan, M. S. (2025) · Acta Diabetologica · doi:10.1007/s00592-024-02438-3 · Cited by 12
Multidimensional analyses of proinsulin peptide-specific regulatory T cells induced by tolerogenic dendritic cells
Suwandi, J. S., Laban, S., Vass, K., Joosten, A. M., van Unen, V., Lelieveldt, B. P. F., Höllt, T., Zwaginga, J. J., Nikolić, T., & Roep, B. O. (2019) · Journal of Autoimmunity · doi:10.1016/j.jaut.2019.102361 · Cited by 12
Augmented Expansion of Treg Cells From Healthy and Autoimmune Subjects via Adult Progenitor Cell Co-Culture
Reading, J. L., Roobrouck, V. D., Hull, C., Becker, P. D., Beyens, J., Valentin-Torres, A., Boardman, D. A., Nova‐Lamperti, E., Stubblefield, S. R., Lombardi, G., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.716606 · Cited by 12
Self-citation
Inhibition of CD226 co-stimulation suppresses diabetes development in the NOD mouse by augmenting regulatory T cells and diminishing effector T cell function
Brown, M. E., Thirawatananond, P., Peters, L. D., Kern, E. J., Vijay, S., Sachs, L. K., Posgai, A. L., Brusko, M., Shapiro, M. R., Mathews, C. E., et al. (2024) · Diabetologia · doi:10.1007/s00125-024-06329-8 · Cited by 13
T helper 17 cells and interleukin-17 immunity in type 1 diabetes: From pathophysiology to targeted immunotherapies
Vasilev, G., Kokudeva, M., Siliogka, E., Padilla, N., Shumnalieva, R., Della‐Morte, D., Ricordi, C., Mihova, A., Infante, M., & Velikova, T. V. (2025) · World Journal of Diabetes · doi:10.4239/wjd.v16.i4.99936 · Cited by 11
The expanding impact of T-regs in the skin
Hajam, E. Y., Panikulam, P., Chu, C.-C., Jayaprakash, H., Majumdar, A., & Jamora, C. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.983700 · Cited by 11

Authors: Hull, C. M., Peakman, M., & Tree, T. I. M.
Affiliations: Guy's Hospital (GB)
Corresponding author: Hull, Caroline M.
Tree, Timothy I. M.
ORCID: Hull, Caroline M.
Peakman, Mark
Tree, Timothy I. M.
Venue: Diabetologia
Publisher: Springer Science and Business Media LLC
Published: 2017-08-02
Volume: 60
Issue: 10
Pages: 1839-1850
ISSN: 0012-186X (ISSN-L)
1432-0428
DOI: 10.1007/s00125-017-4377-1
PMC: PMC6448885
OpenAlex: W2739639576
Cited by: 194
References: 109
Citations by year: 2026: 11 · 2025: 32 · 2024: 30 · 2023: 17 · 2022: 25 · 2021: 25 · 2020: 21 · 2019: 19 · 2018: 13 · 2017: 1
FWCI: 1.89
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (unspecified)
Locations: Diabetologia (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Research Portal (King's College London) (publishedVersion, cc-by)
Funders: King's College London
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Keywords: type 1 diabetes, regulatory T cells, immune tolerance, beta cell destruction, islet autoantigens, CD4+ T cells, CD8+ T cells, thymic selection, peripheral tolerance, Treg dysfunction, Treg therapy, autoimmunity
MeSH terms: Animals, Diabetes Mellitus, Type 1, Humans, Immune Tolerance, T-Lymphocytes, Regulatory

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Regulatory T cell dysfunction in type 1 diabetes: what's broken and how can we fix it?

Abstract

Overview

Integrity signals

Figures

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks