Involvement of Restored Treg Cells in the Immune Pathogenesis of Parkinson’s Disease (PD) Running Title: Immune Pathogenesis of Parkinson’s Disease

Authors

  • Faisal Alkhateeb Ahmad Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt
  • Ahmed Mohamed Mekkawy Department of Cardiothoracic Surgery, Faculty of Medicine, Assiut University Hospitals, Assiut, Egypt
  • Ahmed Ghoneim Department of Cardiothoracic Surgery, Faculty of Medicine, Assiut University Hospitals, Assiut, Egypt
  • Ehab Zahran Department of Cardiothoracic Surgery, Faculty of Medicine, Assiut University Hospitals, Assiut, Egypt
  • Khaled Saad Department of Pediatrics, Faculty of Medicine, Assiut University Children’s Hospital, Assiut, Egypt
  • Ahmad Roshdy Ahmad Department of Pediatrics, College of Medicine, Jouf University, Sakaka, Saudi Arabia
  • Khalid Hashim Mahmoud Department of Pediatrics, Faculty of Medicine, Shaqra University, Dawadmi, Saudi Arabia
  • Eman F. Gad Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt
  • Mohamed Ezzat Department of Pediatrics, Faculty of Medicine, Al Azhar University, Cairo, Egypt
  • Hamad Ghaleb Dailah Research and Scientific Studies Unit, College of Nursing, Jazan University, Jazan, Saudi Arabia
  • Ahmed Nabil Malek Department of Cardiothoracic Surgery, Faculty of Medicine, Assiut University Hospitals, Assiut, Egypt

DOI:

https://doi.org/10.54536/ajmsi.v3i2.3094

Keywords:

Neuro-Degradation, Parkinson’s Disease, Thymic Involution, Pluripotent Stem Cell

Abstract

Neural regression with neuroinflammation and immune dysfunction through neuro-degradative disorder is known as Parkinson’s disease (PD). Parkinson’s disease is a progressive degradative neuronal disorder. In this disease, the continuous depletion of dopaminergic neurons and the existence of protein Lewy bodies are the key points of PD development. In PD patients, regulatory T cells (Tregs) are decreased in number and have an impaired proliferative capacity that affects the suppression of T-cell characteristics. The thymus involution decline in the functionality of T-cell development and consequently naïve T cells makes the immune system more vulnerable to losing its immune surveillance, increasing morbidity and mortality in aged individuals. The persistent process of thymic involution with age vigorously contributes to a progressive reduction in thymic output. Genomic damage, cellular senescence, and epigenetic alterations are the hallmarks of cellular or molecular damage in aging. Therapeutic potential for regeneration of the thymus would improve immunity. Some strategies and approaches have focused on cell-based approaches, technology based on organoid and scaffold modulating of endogenous and exogenous compounds to help in the thymus regeneration, and fabrication technologies that could be used as regenerative approaches. Last but not least the pluripotent stem cell therapies.

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References

Awong, G., Herer, E., Surh, C. D., Dick, J. E., La Motte-Mohs, R. N., & Zúñiga-Pflücker, J. C. (2009). Characterization in vitro and engraftment potential in vivo of human progenitor T cells generated from hematopoietic stem cells. Blood, The Journal of the American Society of Hematology, 114(5), 972-982.

Balestrino, R., & Schapira, A. (2020). Parkinson disease. European journal of neurology, 27(1), 27-42.

Barbouti, A., Vasileiou, P. V., Evangelou, K., Vlasis, K. G., Papoudou-Bai, A., Gorgoulis, V. G., & Kanavaros, P. (2020). Implications of oxidative stress and cellular senescence in age-related thymus involution. Oxidative medicine and cellular longevity, 2020.

Barthlott, T., Handel, A. E., Teh, H. Y., Wirasinha, R. C., Hafen, K., Žuklys, S., Roch, B., Orkin, S. H., de Villartay, J.-P., & Daley, S. R. (2021). Indispensable epigenetic control of thymic epithelial cell development and function by polycomb repressive complex 2. Nature Communications, 12(1), 1-19.

Borgoni, S., Kudryashova, K. S., Burka, K., & de Magalhaes, J. P. (2021). Targeting immune dysfunction in aging. Ageing Research Reviews, 70, 101410.

Bortolomai, I., Sandri, M., Draghici, E., Fontana, E., Campodoni, E., Marcovecchio, G. E., Ferrua, F., Perani, L., Spinelli, A., & Canu, T. (2019). Gene modification and three-dimensional scaffolds as novel tools to allow the use of postnatal thymic epithelial cells for thymus regeneration approaches. Stem cells translational medicine, 8(10), 1107-1122.

Cakala-Jakimowicz, M., Kolodziej-Wojnar, P., & Puzianowska-Kuznicka, M. (2021). Aging-Related Cellular, Structural and Functional Changes in the Lymph Nodes: A Significant Component of Immunosenescence? An Overview. Cells, 10(11), 3148.

Cosway, E. J., James, K. D., Lucas, B., Anderson, G., & White, A. J. (2021). The thymus medulla and its control of αβT cell development. Seminars in immunopathology,

De Cecco, M., Ito, T., Petrashen, A. P., Elias, A. E., Skvir, N. J., Criscione, S. W., Caligiana, A., Brocculi, G., Adney, E. M., & Boeke, J. D. (2019). L1 drives IFN in senescent cells and promotes age-associated inflammation. Nature, 566(7742), 73-78.

Deng, B., Zhang, W., Zhu, Y., Li, Y., Li, D., & Li, B. (2022). FOXP3+ regulatory T cells and age‐related diseases. The FEBS Journal, 289(2), 319-335.

Elsworth, J. D. (2020). Parkinson’s disease treatment: Past, present, and future. Journal of neural transmission, 127(5), 785-791.

Ermolaeva, M., Neri, F., Ori, A., & Rudolph, K. L. (2018). Cellular and epigenetic drivers of stem cell ageing. Nature reviews Molecular cell biology, 19(9), 594-610.

Goldman, J. S. (2019). Predictive genetic counseling for neurodegenerative diseases: past, present, and future. Cold Spring Harbor perspectives in medicine, a036525.

Granadier, D., Iovino, L., Kinsella, S., & Dudakov, J. A. (2021). Dynamics of thymus function and T cell receptor repertoire breadth in health and disease. Seminars in immunopathology.

Guo, Z., Wang, G., Wu, B., Chou, W.-C., Cheng, L., Zhou, C., Lou, J., Wu, D., Su, L., & Zheng, J. (2020). DCAF1 regulates Treg senescence via the ROS axis during immunological aging. The Journal of clinical investigation, 130(11), 5893-5908.

Helgeland, H., Gabrielsen, I., Akselsen, H., Sundaram, A. Y., Flåm, S. T., & Lie, B. A. (2020). Transcriptome profiling of human thymic CD4+ and CD8+ T cells compared to primary peripheral T cells. BMC genomics, 21(1), 1-15.

Kadouri, N., Nevo, S., Goldfarb, Y., & Abramson, J. (2020). Thymic epithelial cell heterogeneity: TEC by TEC. Nature Reviews Immunology, 20(4), 239-253.

Kim, T. W., Koo, S. Y., & Studer, L. (2020). Pluripotent stem cell therapies for Parkinson disease: present challenges and future opportunities. Frontiers in Cell and Developmental Biology, 729.

Kisielow, P. (2019). How does the immune system learn to distinguish between good and evil? The first definitive studies of T cell central tolerance and positive selection. Immunogenetics, 71(8), 513-518.

Knight, J. (2021). Endocrine system 5: pineal and thymus glands. Nursing Times, 117, 9-54.

Liu, J., He, J., Huang, Y., & Hu, Z. (2020). Effect of Bone Marrow Stromal Cells in Parkinson’s Disease Rodent Model: A Meta-Analysis. Frontiers in aging neuroscience, 12, 463.

Mas-Bargues, C., Borrás, C., & Viña, J. (2021). Bcl-xL as a Modulator of Senescence and Aging. International Journal of Molecular Sciences, 22(4), 1527.

Miri, N. S., Saadat, P., Azadmehr, A., Oladnabi, M., & Daraei, A. (2020). Toll-Like Receptor (TLR)-9 rs352140 Polymorphism is an Immunopathology Protective Factor in Parkinson’s Disease in the Northern Iranian Population. Iranian Journal of Immunology, 17(4), 313-323.

Mittelbrunn, M., & Kroemer, G. (2021). Hallmarks of T cell aging. Nature Immunology, 22(6), 687-698.

Montel-Hagen, A., Seet, C. S., Li, S., Chick, B., Zhu, Y., Chang, P., Tsai, S., Sun, V., Lopez, S., & Chen, H.-C. (2019). Organoid-induced differentiation of conventional T cells from human pluripotent stem cells. Cell stem cell, 24(3), 376-389. e378.

Otsuka, R., Wada, H., Tsuji, H., Sasaki, A., Murata, T., Itoh, M., Baghdadi, M., & Seino, K.-i. (2020). Efficient generation of thymic epithelium from induced pluripotent stem cells that prolongs allograft survival. Scientific reports, 10(1), 1-8.

Pansarasa, O., Pistono, C., Davin, A., Bordoni, M., Mimmi, M. C., Guaita, A., & Cereda, C. (2019). Altered immune system in frailty: genetics and diet may influence inflammation. Ageing Research Reviews, 54, 100935.

Park, J.-E., Botting, R. A., Domínguez Conde, C., Popescu, D.-M., Lavaert, M., Kunz, D. J., Goh, I., Stephenson, E., Ragazzini, R., & Tuck, E. (2020). A cell atlas of human thymic development defines T cell repertoire formation. Science, 367(6480), eaay3224.

Rezzani, R., Franco, C., Hardeland, R., & Rodella, L. F. (2020). Thymus-pineal gland axis: revisiting its role in human life and ageing. International Journal of Molecular Sciences, 21(22), 8806.

Schulz, M., Salamero-Boix, A., Niesel, K., Alekseeva, T., & Sevenich, L. (2019). Microenvironmental regulation of tumor progression and therapeutic response in brain metastasis. Frontiers in immunology, 1713.

Schwab, A. D., Thurston, M. J., Machhi, J., Olson, K. E., Namminga, K. L., Gendelman, H. E., & Mosley, R. L. (2020). Immunotherapy for Parkinson’s disease. Neurobiology of disease, 137, 104760.

Seet, C. S., He, C., Bethune, M. T., Li, S., Chick, B., Gschweng, E. H., Zhu, Y., Kim, K., Kohn, D. B., & Baltimore, D. (2017). Generation of mature T cells from human hematopoietic stem and progenitor cells in artificial thymic organoids. Nature methods, 14(5), 521-530.

Sekai, M., Wang, J., Minato, N., & Hamazaki, Y. (2019). An improved clonogenic culture method for thymic epithelial cells. Journal of immunological methods, 467, 29-36.

Sergi, C. M. (2020). Hematolymphoid System. In Pathology of Childhood and Adolescence (pp. 861-931). Springer.

Shah, K., Al-Haidari, A., Sun, J., & Kazi, J. U. (2021). T cell receptor (TCR) signaling in health and disease. Signal transduction and targeted therapy, 6(1), 1-26.

Sharma, H., & Moroni, L. (2021). Recent Advancements in Regenerative Approaches for Thymus Rejuvenation. Advanced Science, 8(14), 2100543. https://doi.org/https://doi.org/10.1002/advs.202100543

Smith, A. L., & Göbel, T. W. (2022). Avian T cells: antigen recognition and lineages. In Avian immunology (pp. 121-134). Elsevier.

Srinivasan, J., Lancaster, J. N., Singarapu, N., Hale, L. P., Ehrlich, L. I., & Richie, E. R. (2021). Age-related changes in Thymic central tolerance. Frontiers in immunology, 12, 1353.

Su, M., Hu, R., Jin, J., Yan, Y., Song, Y., Sullivan, R., & Lai, L. (2015). Efficient in vitro generation of functional thymic epithelial progenitors from human embryonic stem cells. Scientific reports, 5(1), 1-8.

Thome, A. D., Atassi, F., Wang, J., Faridar, A., Zhao, W., Thonhoff, J. R., Beers, D. R., Lai, E. C., & Appel, S. H. (2021). Ex vivo expansion of dysfunctional regulatory T lymphocytes restores suppressive function in Parkinson’s disease. NPJ Parkinson’s disease, 7(1), 1-12.

Varadé, J., Magadán, S., & González-Fernández, Á. (2021). Human immunology and immunotherapy: main achievements and challenges. Cellular & Molecular Immunology, 18(4), 805-828.

Velardi, E., Tsai, J. J., & van den Brink, M. R. (2021). T cell regeneration after immunological injury. Nature Reviews Immunology, 21(5), 277-291.

Wiertsema, S. P., van Bergenhenegouwen, J., Garssen, J., & Knippels, L. M. (2021). The interplay between the gut microbiome and the immune system in the context of infectious diseases throughout life and the role of nutrition in optimizing treatment strategies. Nutrients, 13(3), 886.

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Published

2024-07-03

How to Cite

Ahmad, F. A., Mekkawy, A. M., Ghoneim, A., Zahran, E., Saad, K., Ahmad, A. R., Mahmoud, K. H., Gad, E. F., Ezzat, M., Dailah, H. G., & Malek, A. N. (2024). Involvement of Restored Treg Cells in the Immune Pathogenesis of Parkinson’s Disease (PD) Running Title: Immune Pathogenesis of Parkinson’s Disease. American Journal of Medical Science and Innovation, 3(2), 12–17. https://doi.org/10.54536/ajmsi.v3i2.3094