Dysfunction of Regulatory T Cells: The Fundamental Underlying Mechanisms Underpinning Autoimmune Diseases
##plugins.themes.bootstrap3.article.main##
##plugins.themes.bootstrap3.article.sidebar##
Published
Mar 31, 2025
Abstract
Regulatory T cells (Tregs) play a critical role in maintaining immune homeostasis by suppressing excessive immune responses and preventing autoimmune reactions. Dysregulation of Treg function has been identified as a key factor in the development and progression of various autoimmune diseases. Understanding the fundamental mechanisms underlying Treg dysfunction is essential for unraveling the complex pathogenesis of autoimmune disorders. This article delves into the intricate interplay between Tregs and autoimmune diseases, exploring the impact of Treg dysfunction on immune regulation and disease development. By examining the mechanisms of Treg dysfunction and therapeutic strategies aimed at restoring Treg function, we aim to shed light on this intricate aspect of autoimmunity and pave the way for innovative approaches to managing autoimmune conditions.
##plugins.themes.bootstrap3.article.details##
Keywords
Regulatory T Cells, Dysfunction, Autoimmune Diseases, Mechanisms, Therapeutic Potential
Supporting Agencies
No funding source declared.
References
Ajith, A., Merimi, M., Arki, M. K., Hossein-Khannazer, N., Najar, M., Vosough, M., Sokal, E. M., & Najimi, M. (2024). Immune regulation and therapeutic application of T regulatory cells in liver diseases. Frontiers in Immunology, 15. https://doi.org/10.3389/fimmu.2024.1371089
Bayati, F., Mohammadi, M., Valadi, M., Jamshidi, S., Foma, A. M., & Sharif-Paghaleh, E. (2021). The therapeutic potential of regulatory T cells: challenges and opportunities. Frontiers in Immunology, 11. https://doi.org/10.3389/fimmu.2020.585819
Bednar, K. J., Lee, J. H., & Ort, T. (2022). Tregs in Autoimmunity: Insights into intrinsic brake mechanism driving pathogenesis and immune homeostasis. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.932485
Chan, E., & Mani, A. R. (2025). Assessing the therapeutic potential of vagus nerve stimulation in autoimmune diseases: A systematic review. Physiological Reports, 13(3). https://doi.org/10.14814/phy2.70230
De La Rosa, M., Rutz, S., Dorninger, H., & Scheffold, A. (2004). Interleukin‐2 is essential for CD4+CD25+ regulatory T cell function. European Journal of Immunology, 34(9), 2480–2488. https://doi.org/10.1002/eji.200425274
Deng, G., Song, X., Fujimoto, S., Piccirillo, C. A., Nagai, Y., & Greene, M. I. (2019). FOXP3 post-translational modifications and TREG suppressive activity. Frontiers in Immunology, 10. https://doi.org/10.3389/fimmu.2019.02486
Elenkov, I. J., & Chrousos, G. P. (2002). Stress hormones, proinflammatory and antiinflammatory cytokines, and autoimmunity. Annals of the New York Academy of Sciences, 966(1), 290–303. https://doi.org/10.1111/j.1749-6632.2002.tb04229.x
Ezzedine, K., Tannous, R., Pearson, T. F., & Harris, J. E. (2025). Recent clinical and mechanistic insights into vitiligo offer new treatment options for cell-specific autoimmunity. Journal of Clinical Investigation, 135(2). https://doi.org/10.1172/jci185785
Fasching, P., Stradner, M., Graninger, W., Dejaco, C., & Fessler, J. (2017). Therapeutic potential of targeting the TH17/TREG axis in autoimmune disorders. Molecules, 22(1), 134. https://doi.org/10.3390/molecules22010134
Gol-Ara, M., Jadidi-Niaragh, F., Sadria, R., Azizi, G., & Mirshafiey, A. (2012). The role of different subsets of regulatory T cells in immunopathogenesis of rheumatoid arthritis. Arthritis, 2012, 1–16. https://doi.org/10.1155/2012/805875
Hardtke-Wolenski, M., & Landwehr-Kenzel, S. (2024). Tipping the balance in autoimmunity: are regulatory t cells the cause, the cure, or both? Molecular and Cellular Pediatrics, 11(1). https://doi.org/10.1186/s40348-024-00176-8
Harris, F., Berdugo, Y. A., & Tree, T. (2022). IL-2-based approaches to Treg enhancement. Clinical & Experimental Immunology, 211(2), 149–163. https://doi.org/10.1093/cei/uxac105
Hippen, K. L., Loschi, M., Nicholls, J., MacDonald, K. P. A., & Blazar, B. R. (2018). Effects of MicroRNA on regulatory T cells and implications for adoptive cellular therapy to ameliorate Graft-versus-Host disease. Frontiers in Immunology, 9. https://doi.org/10.3389/fimmu.2018.00057
Honing, D. Y., Luiten, R. M., & Matos, T. R. (2024). Regulatory T cell dysfunction in autoimmune diseases. International Journal of Molecular Sciences, 25(13), 7171. https://doi.org/10.3390/ijms25137171
Hossen, M. M., Ma, Y., Yin, Z., Xia, Y., Du, J., Huang, J. Y., Huang, J. J., Zou, L., Ye, Z., & Huang, Z. (2023). Current understanding of CTLA-4: from mechanism to autoimmune diseases. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1198365
Huang, F., & Sattler, S. (2011). Regulatory T cell deficiency in systemic autoimmune disorders – causal relationship and underlying immunological mechanisms. In InTech eBooks. https://doi.org/10.5772/21297
Huang, W., Li, Y., Chen, P., Sheng-Kai, K., MA, & Wang, L. (2025). Mesenchymal stem cell therapy as a game-changer in liver diseases: review of current clinical trials. Stem Cell Research & Therapy, 16(1). https://doi.org/10.1186/s13287-024-04127-y
Humrich, J. Y., Morbach, H., Undeutsch, R., Enghard, P., Rosenberger, S., Weigert, O., Kloke, L., Heimann, J., Gaber, T., Brandenburg, S., Scheffold, A., Huehn, J., Radbruch, A., Burmester, G., & Riemekasten, G. (2009). Homeostatic imbalance of regulatory and effector T cells due to IL-2 deprivation amplifies murine lupus. Proceedings of the National Academy of Sciences, 107(1), 204–209. https://doi.org/10.1073/pnas.0903158107
Issazadeh-Navikas, S., Teimer, R., & Bockermann, R. (2011). Influence of dietary components on regulatory T cells. Molecular Medicine, 18(1), 95–110. https://doi.org/10.2119/molmed.2011.00311
Kennedy-Batalla, R., Acevedo, D., Luo, Y., Esteve-Solé, A., Vlagea, A., Correa-Rocha, R., Seoane-Reula, M. E., & Alsina, L. (2024). Treg in inborn errors of immunity: gaps, knowns and future perspectives. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1278759
Khare, T., Liu, K., Chilambe, L. O., & Khare, S. (2025). NAFLD and NAFLD related HCC: Emerging treatments and clinical trials. International Journal of Molecular Sciences, 26(1), 306. https://doi.org/10.3390/ijms26010306
Lal, G., Zhang, N., Van Der Touw, W., Ding, Y., Ju, W., Bottinger, E. P., Reid, S. P., Levy, D. E., & Bromberg, J. S. (2009). Epigenetic regulation of FOXP3 expression in regulatory T cells by DNA methylation. The Journal of Immunology, 182(1), 259–273. https://doi.org/10.4049/jimmunol.182.1.259
Lehto, M., & Groop, P. (2018). The Gut-Kidney Axis: Putative interconnections between gastrointestinal and renal disorders. Frontiers in Endocrinology, 9. https://doi.org/10.3389/fendo.2018.00553
Li, F., Xu, J., Zheng, J., Sokolove, J., Zhu, K., Zhang, Y., Sun, H., Evangelou, E., & Pan, Z. (2014). Association between Interleukin-6 Gene Polymorphisms and Rheumatoid Arthritis in Chinese Han Population: A Case-Control Study and A Meta-analysis. Scientific Reports, 4(1). https://doi.org/10.1038/srep05714
Li, S., Gowans, E. J., Chougnet, C., Plebanski, M., & Dittmer, U. (2007). Natural regulatory T cells and persistent viral infection. Journal of Virology, 82(1), 21–30. https://doi.org/10.1128/jvi.01768-07
Li, Y., Ye, R., Dai, H., Lin, J., Cheng, Y., Zhou, Y., & Lu, Y. (2025). Exploring TNFR1: from discovery to targeted therapy development. Journal of Translational Medicine, 23(1). https://doi.org/10.1186/s12967-025-06122-0
Loh, M., Zhou, L., Ng, H. K., & Chambers, J. C. (2019). Epigenetic disturbances in obesity and diabetes: Epidemiological and functional insights. Molecular Metabolism, 27, S33–S41. https://doi.org/10.1016/j.molmet.2019.06.011
Luo, A., Leach, S. T., Barres, R., Hesson, L. B., Grimm, M. C., & Simar, D. (2017). The microbiota and epigenetic regulation of T Helper 17/Regulatory T cells: in search of a balanced immune system. Frontiers in Immunology, 8. https://doi.org/10.3389/fimmu.2017.00417
Maier, L. M., Anderson, D. E., De Jager, P. L., Wicker, L. S., & Hafler, D. A. (2007). Allelic variant inCTLA4alters T cell phosphorylation patterns. Proceedings of the National Academy of Sciences, 104(47), 18607–18612. https://doi.org/10.1073/pnas.0706409104
Maier, L. M., Lowe, C. E., Cooper, J., Downes, K., Anderson, D. E., Severson, C., Clark, P. M., Healy, B., Walker, N., Aubin, C., Oksenberg, J. R., Hauser, S. L., Compston, A., Sawcer, S., De Jager, P. L., Wicker, L. S., Todd, J. A., & Hafler, D. A. (2009). IL2RA
genetic heterogeneity in multiple sclerosis and type 1 diabetes susceptibility and soluble interleukin-2 receptor production. PLoS Genetics, 5(1), e1000322. https://doi.org/10.1371/journal.pgen.1000322
Malek, T. R., & Castro, I. (2010). Interleukin-2 Receptor Signaling: At the Interface between Tolerance and Immunity. Immunity, 33(2), 153–165. https://doi.org/10.1016/j.immuni.2010.08.004
Ohkura, N., Hamaguchi, M., & Sakaguchi, S. (2011). FOXP3+ regulatory T cells: control of FOXP3 expression by pharmacological agents. Trends in Pharmacological Sciences, 32(3), 158–166. https://doi.org/10.1016/j.tips.2010.12.004
Olson, B. M., Sullivan, J. A., & Burlingham, W. J. (2013). Interleukin 35: a key mediator of suppression and the propagation of infectious tolerance. Frontiers in Immunology, 4. https://doi.org/10.3389/fimmu.2013.00315
Omenetti, S., & Pizarro, T. T. (2015). The TREG/TH17 axis: a dynamic balance regulated by the gut microbiome. Frontiers in Immunology, 6. https://doi.org/10.3389/fimmu.2015.00639
Oparaugo, N. C., Ouyang, K., Nguyen, N. P. N., Nelson, A. M., & Agak, G. W. (2023). Human Regulatory T cells: Understanding the role of TrEgs in select autoimmune skin diseases and Post-Transplant nonmelanoma skin cancers. International Journal of Molecular Sciences, 24(2), 1527. https://doi.org/10.3390/ijms24021527
Perdigoto, A. L., Chatenoud, L., Bluestone, J. A., & Herold, K. C. (2016). Inducing and administering Tregs to treat human disease. Frontiers in Immunology, 6. https://doi.org/10.3389/fimmu.2015.00654
Plitas, G., & Rudensky, A. Y. (2016). Regulatory T cells: differentiation and function. Cancer Immunology Research, 4(9), 721–725. https://doi.org/10.1158/2326-6066.cir-16-0193
Rao, D. N., & Naqvi, R. A. (2011). FOXP3: a key player in T regulatory biology. Indian Journal of Clinical Biochemistry, 26(1), 1–2. https://doi.org/10.1007/s12291-011-0112-8
Richert-Spuhler, L. E., & Lund, J. M. (2015). The immune fulcrum. Progress in Molecular Biology and Translational Science, 217–243. https://doi.org/10.1016/bs.pmbts.2015.07.015
Ryba-Stanisławowska, M., Skrzypkowska, M., Myśliwska, J., & Myśliwiec, M. (2013). The Serum IL-6 Profile and Treg/Th17 Peripheral Cell Populations in Patients with Type 1 Diabetes. Mediators of Inflammation, 2013, 1–7. https://doi.org/10.1155/2013/205284
Schlöder, J., Shahneh, F., Schneider, F., & Wieschendorf, B. (2022). Boosting regulatory T cell function for the treatment of autoimmune diseases – That’s only half the battle! Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.973813
Schmitt, E. G., & Williams, C. B. (2013). Generation and function of induced regulatory T cells. Frontiers in Immunology, 4. https://doi.org/10.3389/fimmu.2013.00152
Schwab, E., Annaldas, B., Ramesh, N., Lundberg, A., Shelke, V., Xu, X., Gilbertson, C., Byun, J., & Lam, E. T. (2025). Fully automated CTC detection, segmentation and classification for multi-channel IF imaging. In Lecture notes in computer science (pp. 55–65). https://doi.org/10.1007/978-3-031-77786-8_6
Simopoulos, A. P. (2002). Omega-3 fatty acids in inflammation and autoimmune diseases. Journal of the American College of Nutrition, 21(6), 495–505. https://doi.org/10.1080/07315724.2002.10719248
Smith, D. A., & Germolec, D. R. (1999). Introduction to immunology and autoimmunity. Environmental Health Perspectives, 107(suppl 5), 661–665. https://doi.org/10.1289/ehp.99107s5661
Sumida, T. S., Cheru, N. T., & Hafler, D. A. (2024). The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases. Nature Reviews. Immunology, 24(7), 503–517. https://doi.org/10.1038/s41577-024-00994-x
Yang, Y. (2023). T regulatory Function and Modification for Future Application. SHS Web of Conferences, 174, 03006. https://doi.org/10.1051/shsconf/202317403006
Yoshimura, A., Mori, H., Ohishi, M., Aki, D., & Hanada, T. (2003). Negative regulation of cytokine signaling influences inflammation. Current Opinion in Immunology, 15(6), 704–708. https://doi.org/10.1016/j.coi.2003.09.004
Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023). Role of neuroinflammation in neurodegeneration development. Signal Transduction and Targeted Therapy, 8(1). https://doi.org/10.1038/s41392-023-01486-5
Zhao, J., Wei, K., Chang, C., Xu, L., Jiang, P., Guo, S., Schrodi, S. J., & He, D. (2022). DNA methylation of T lymphocytes as a therapeutic target: Implications for Rheumatoid arthritis etiology. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.863703
Bayati, F., Mohammadi, M., Valadi, M., Jamshidi, S., Foma, A. M., & Sharif-Paghaleh, E. (2021). The therapeutic potential of regulatory T cells: challenges and opportunities. Frontiers in Immunology, 11. https://doi.org/10.3389/fimmu.2020.585819
Bednar, K. J., Lee, J. H., & Ort, T. (2022). Tregs in Autoimmunity: Insights into intrinsic brake mechanism driving pathogenesis and immune homeostasis. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.932485
Chan, E., & Mani, A. R. (2025). Assessing the therapeutic potential of vagus nerve stimulation in autoimmune diseases: A systematic review. Physiological Reports, 13(3). https://doi.org/10.14814/phy2.70230
De La Rosa, M., Rutz, S., Dorninger, H., & Scheffold, A. (2004). Interleukin‐2 is essential for CD4+CD25+ regulatory T cell function. European Journal of Immunology, 34(9), 2480–2488. https://doi.org/10.1002/eji.200425274
Deng, G., Song, X., Fujimoto, S., Piccirillo, C. A., Nagai, Y., & Greene, M. I. (2019). FOXP3 post-translational modifications and TREG suppressive activity. Frontiers in Immunology, 10. https://doi.org/10.3389/fimmu.2019.02486
Elenkov, I. J., & Chrousos, G. P. (2002). Stress hormones, proinflammatory and antiinflammatory cytokines, and autoimmunity. Annals of the New York Academy of Sciences, 966(1), 290–303. https://doi.org/10.1111/j.1749-6632.2002.tb04229.x
Ezzedine, K., Tannous, R., Pearson, T. F., & Harris, J. E. (2025). Recent clinical and mechanistic insights into vitiligo offer new treatment options for cell-specific autoimmunity. Journal of Clinical Investigation, 135(2). https://doi.org/10.1172/jci185785
Fasching, P., Stradner, M., Graninger, W., Dejaco, C., & Fessler, J. (2017). Therapeutic potential of targeting the TH17/TREG axis in autoimmune disorders. Molecules, 22(1), 134. https://doi.org/10.3390/molecules22010134
Gol-Ara, M., Jadidi-Niaragh, F., Sadria, R., Azizi, G., & Mirshafiey, A. (2012). The role of different subsets of regulatory T cells in immunopathogenesis of rheumatoid arthritis. Arthritis, 2012, 1–16. https://doi.org/10.1155/2012/805875
Hardtke-Wolenski, M., & Landwehr-Kenzel, S. (2024). Tipping the balance in autoimmunity: are regulatory t cells the cause, the cure, or both? Molecular and Cellular Pediatrics, 11(1). https://doi.org/10.1186/s40348-024-00176-8
Harris, F., Berdugo, Y. A., & Tree, T. (2022). IL-2-based approaches to Treg enhancement. Clinical & Experimental Immunology, 211(2), 149–163. https://doi.org/10.1093/cei/uxac105
Hippen, K. L., Loschi, M., Nicholls, J., MacDonald, K. P. A., & Blazar, B. R. (2018). Effects of MicroRNA on regulatory T cells and implications for adoptive cellular therapy to ameliorate Graft-versus-Host disease. Frontiers in Immunology, 9. https://doi.org/10.3389/fimmu.2018.00057
Honing, D. Y., Luiten, R. M., & Matos, T. R. (2024). Regulatory T cell dysfunction in autoimmune diseases. International Journal of Molecular Sciences, 25(13), 7171. https://doi.org/10.3390/ijms25137171
Hossen, M. M., Ma, Y., Yin, Z., Xia, Y., Du, J., Huang, J. Y., Huang, J. J., Zou, L., Ye, Z., & Huang, Z. (2023). Current understanding of CTLA-4: from mechanism to autoimmune diseases. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1198365
Huang, F., & Sattler, S. (2011). Regulatory T cell deficiency in systemic autoimmune disorders – causal relationship and underlying immunological mechanisms. In InTech eBooks. https://doi.org/10.5772/21297
Huang, W., Li, Y., Chen, P., Sheng-Kai, K., MA, & Wang, L. (2025). Mesenchymal stem cell therapy as a game-changer in liver diseases: review of current clinical trials. Stem Cell Research & Therapy, 16(1). https://doi.org/10.1186/s13287-024-04127-y
Humrich, J. Y., Morbach, H., Undeutsch, R., Enghard, P., Rosenberger, S., Weigert, O., Kloke, L., Heimann, J., Gaber, T., Brandenburg, S., Scheffold, A., Huehn, J., Radbruch, A., Burmester, G., & Riemekasten, G. (2009). Homeostatic imbalance of regulatory and effector T cells due to IL-2 deprivation amplifies murine lupus. Proceedings of the National Academy of Sciences, 107(1), 204–209. https://doi.org/10.1073/pnas.0903158107
Issazadeh-Navikas, S., Teimer, R., & Bockermann, R. (2011). Influence of dietary components on regulatory T cells. Molecular Medicine, 18(1), 95–110. https://doi.org/10.2119/molmed.2011.00311
Kennedy-Batalla, R., Acevedo, D., Luo, Y., Esteve-Solé, A., Vlagea, A., Correa-Rocha, R., Seoane-Reula, M. E., & Alsina, L. (2024). Treg in inborn errors of immunity: gaps, knowns and future perspectives. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1278759
Khare, T., Liu, K., Chilambe, L. O., & Khare, S. (2025). NAFLD and NAFLD related HCC: Emerging treatments and clinical trials. International Journal of Molecular Sciences, 26(1), 306. https://doi.org/10.3390/ijms26010306
Lal, G., Zhang, N., Van Der Touw, W., Ding, Y., Ju, W., Bottinger, E. P., Reid, S. P., Levy, D. E., & Bromberg, J. S. (2009). Epigenetic regulation of FOXP3 expression in regulatory T cells by DNA methylation. The Journal of Immunology, 182(1), 259–273. https://doi.org/10.4049/jimmunol.182.1.259
Lehto, M., & Groop, P. (2018). The Gut-Kidney Axis: Putative interconnections between gastrointestinal and renal disorders. Frontiers in Endocrinology, 9. https://doi.org/10.3389/fendo.2018.00553
Li, F., Xu, J., Zheng, J., Sokolove, J., Zhu, K., Zhang, Y., Sun, H., Evangelou, E., & Pan, Z. (2014). Association between Interleukin-6 Gene Polymorphisms and Rheumatoid Arthritis in Chinese Han Population: A Case-Control Study and A Meta-analysis. Scientific Reports, 4(1). https://doi.org/10.1038/srep05714
Li, S., Gowans, E. J., Chougnet, C., Plebanski, M., & Dittmer, U. (2007). Natural regulatory T cells and persistent viral infection. Journal of Virology, 82(1), 21–30. https://doi.org/10.1128/jvi.01768-07
Li, Y., Ye, R., Dai, H., Lin, J., Cheng, Y., Zhou, Y., & Lu, Y. (2025). Exploring TNFR1: from discovery to targeted therapy development. Journal of Translational Medicine, 23(1). https://doi.org/10.1186/s12967-025-06122-0
Loh, M., Zhou, L., Ng, H. K., & Chambers, J. C. (2019). Epigenetic disturbances in obesity and diabetes: Epidemiological and functional insights. Molecular Metabolism, 27, S33–S41. https://doi.org/10.1016/j.molmet.2019.06.011
Luo, A., Leach, S. T., Barres, R., Hesson, L. B., Grimm, M. C., & Simar, D. (2017). The microbiota and epigenetic regulation of T Helper 17/Regulatory T cells: in search of a balanced immune system. Frontiers in Immunology, 8. https://doi.org/10.3389/fimmu.2017.00417
Maier, L. M., Anderson, D. E., De Jager, P. L., Wicker, L. S., & Hafler, D. A. (2007). Allelic variant inCTLA4alters T cell phosphorylation patterns. Proceedings of the National Academy of Sciences, 104(47), 18607–18612. https://doi.org/10.1073/pnas.0706409104
Maier, L. M., Lowe, C. E., Cooper, J., Downes, K., Anderson, D. E., Severson, C., Clark, P. M., Healy, B., Walker, N., Aubin, C., Oksenberg, J. R., Hauser, S. L., Compston, A., Sawcer, S., De Jager, P. L., Wicker, L. S., Todd, J. A., & Hafler, D. A. (2009). IL2RA
genetic heterogeneity in multiple sclerosis and type 1 diabetes susceptibility and soluble interleukin-2 receptor production. PLoS Genetics, 5(1), e1000322. https://doi.org/10.1371/journal.pgen.1000322
Malek, T. R., & Castro, I. (2010). Interleukin-2 Receptor Signaling: At the Interface between Tolerance and Immunity. Immunity, 33(2), 153–165. https://doi.org/10.1016/j.immuni.2010.08.004
Ohkura, N., Hamaguchi, M., & Sakaguchi, S. (2011). FOXP3+ regulatory T cells: control of FOXP3 expression by pharmacological agents. Trends in Pharmacological Sciences, 32(3), 158–166. https://doi.org/10.1016/j.tips.2010.12.004
Olson, B. M., Sullivan, J. A., & Burlingham, W. J. (2013). Interleukin 35: a key mediator of suppression and the propagation of infectious tolerance. Frontiers in Immunology, 4. https://doi.org/10.3389/fimmu.2013.00315
Omenetti, S., & Pizarro, T. T. (2015). The TREG/TH17 axis: a dynamic balance regulated by the gut microbiome. Frontiers in Immunology, 6. https://doi.org/10.3389/fimmu.2015.00639
Oparaugo, N. C., Ouyang, K., Nguyen, N. P. N., Nelson, A. M., & Agak, G. W. (2023). Human Regulatory T cells: Understanding the role of TrEgs in select autoimmune skin diseases and Post-Transplant nonmelanoma skin cancers. International Journal of Molecular Sciences, 24(2), 1527. https://doi.org/10.3390/ijms24021527
Perdigoto, A. L., Chatenoud, L., Bluestone, J. A., & Herold, K. C. (2016). Inducing and administering Tregs to treat human disease. Frontiers in Immunology, 6. https://doi.org/10.3389/fimmu.2015.00654
Plitas, G., & Rudensky, A. Y. (2016). Regulatory T cells: differentiation and function. Cancer Immunology Research, 4(9), 721–725. https://doi.org/10.1158/2326-6066.cir-16-0193
Rao, D. N., & Naqvi, R. A. (2011). FOXP3: a key player in T regulatory biology. Indian Journal of Clinical Biochemistry, 26(1), 1–2. https://doi.org/10.1007/s12291-011-0112-8
Richert-Spuhler, L. E., & Lund, J. M. (2015). The immune fulcrum. Progress in Molecular Biology and Translational Science, 217–243. https://doi.org/10.1016/bs.pmbts.2015.07.015
Ryba-Stanisławowska, M., Skrzypkowska, M., Myśliwska, J., & Myśliwiec, M. (2013). The Serum IL-6 Profile and Treg/Th17 Peripheral Cell Populations in Patients with Type 1 Diabetes. Mediators of Inflammation, 2013, 1–7. https://doi.org/10.1155/2013/205284
Schlöder, J., Shahneh, F., Schneider, F., & Wieschendorf, B. (2022). Boosting regulatory T cell function for the treatment of autoimmune diseases – That’s only half the battle! Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.973813
Schmitt, E. G., & Williams, C. B. (2013). Generation and function of induced regulatory T cells. Frontiers in Immunology, 4. https://doi.org/10.3389/fimmu.2013.00152
Schwab, E., Annaldas, B., Ramesh, N., Lundberg, A., Shelke, V., Xu, X., Gilbertson, C., Byun, J., & Lam, E. T. (2025). Fully automated CTC detection, segmentation and classification for multi-channel IF imaging. In Lecture notes in computer science (pp. 55–65). https://doi.org/10.1007/978-3-031-77786-8_6
Simopoulos, A. P. (2002). Omega-3 fatty acids in inflammation and autoimmune diseases. Journal of the American College of Nutrition, 21(6), 495–505. https://doi.org/10.1080/07315724.2002.10719248
Smith, D. A., & Germolec, D. R. (1999). Introduction to immunology and autoimmunity. Environmental Health Perspectives, 107(suppl 5), 661–665. https://doi.org/10.1289/ehp.99107s5661
Sumida, T. S., Cheru, N. T., & Hafler, D. A. (2024). The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases. Nature Reviews. Immunology, 24(7), 503–517. https://doi.org/10.1038/s41577-024-00994-x
Yang, Y. (2023). T regulatory Function and Modification for Future Application. SHS Web of Conferences, 174, 03006. https://doi.org/10.1051/shsconf/202317403006
Yoshimura, A., Mori, H., Ohishi, M., Aki, D., & Hanada, T. (2003). Negative regulation of cytokine signaling influences inflammation. Current Opinion in Immunology, 15(6), 704–708. https://doi.org/10.1016/j.coi.2003.09.004
Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023). Role of neuroinflammation in neurodegeneration development. Signal Transduction and Targeted Therapy, 8(1). https://doi.org/10.1038/s41392-023-01486-5
Zhao, J., Wei, K., Chang, C., Xu, L., Jiang, P., Guo, S., Schrodi, S. J., & He, D. (2022). DNA methylation of T lymphocytes as a therapeutic target: Implications for Rheumatoid arthritis etiology. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.863703
How to Cite
Walczak, S. (2025). Dysfunction of Regulatory T Cells: The Fundamental Underlying Mechanisms Underpinning Autoimmune Diseases. Science Insights, 46(3), 1777–1786. https://doi.org/10.15354/si.25.re1160
Issue
Section
Review
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.