The Balance of Th17/Treg Cells at The Ocular Surface in Dry Eye Disease

Yıl 2022, Cilt: 4 Sayı: 3, 158 - 166, 31.12.2022

Eman Alhardode , E. Ümit Bağrıaçık

Öz

The eye is considered immune-privileged along with the brain and the testicles. To preserve their visual function, a state of tolerogenic microenvironment must be sustained by the resident immune cells to prevent aggressive inflammatory reactions. Excessive immune system stimulation or immunoregulatory mechanisms disruption at the ocular surface can result in inflammation, subsequently leading to ocular surface diseases. Dry eye is the most common type of ocular surface disorders which is characterized by unstable tear film and a variety of symptoms that adversely affects the daily activities of the patient. Despite the multifactorial nature of the dry eye, recent studies have shown that immunologic processes have a critical role in the disease's pathogenesis and progression. Herein, we focused on the involvement of Th17 and Tregs in the disease's pathophysiology and their relation to the disease progression.

Anahtar Kelimeler

Th17, Treg, Dry Eye, Hyperosmolarity, Inflammation.

Kaynakça

• Adyanthaya, S., & Abhilash, B. (2021). Dry eye disease-are we underselling it? An epidemic in the offing and future management trends. Int J Med Opthamol, 3, 41-43.‏
• Aghbash, P. S., Hemmat, N., Nahand, J. S., Shamekh, A., Memar, M. Y., Babaei, A., & Baghi, H. B. (2021). The role of Th17 cells in viral infections. International Immunopharmacology, 91, 107331.‏
• Akpek, E. K., Bunya, V. Y., & Saldanha, I. J. (2019). Sjögren’s syndrome: more than just dry eye. Cornea, 38(5), 658.‏
• Alharbi, O. O., Beyari, G. M., Saber, W. A., Alotaibi, A. F., Bukannan, A. Y., & Mohamed, Y. N. (2020). Etiology, prevalence, risk factors, and treatment of dry eye disease. Int J Med Develop Countr, 4(1), 137-142.‏).
• Alvarez, F., Al‐Aubodah, T. A., Yang, Y. H., & Piccirillo, C. A. (2020). Mechanisms of TREG cell adaptation to inflammation. Journal of leukocyte biology, 108(2), 559-571.‏
• Baiula, M., & Spampinato, S. (2021). Experimental Pharmacotherapy for Dry Eye Disease: A Review. Journal of experimental pharmacology, 13, 345–358. https://doi.org/10.2147/JEP.S237487).
• Barabino, S., Aragona, P., di Zazzo, A., Rolando, M., & with the contribution of selected ocular surface experts from the Società Italiana di Dacriologia e Superficie Oculare. (2021). Updated definition and classification of dry eye disease: Renewed proposals using the nominal group and Delphi techniques. European Journal of Ophthalmology, 31(1), 42-48.‏)
• Cano, R. L. E., & Lopera, H. D. E. (2013). Introduction to T and B lymphocytes. In Autoimmunity: From Bench to Bedside [Internet]. El Rosario University Press.‏
• Chauhan, S. K., El Annan, J., Ecoiffier, T., Goyal, S., Zhang, Q., Saban, D. R., & Dana, R. (2009). Autoimmunity in dry eye is due to resistance of Th17 to Treg suppression. The Journal of Immunology, 182(3), 1247-1252.‏
• Chen, Y., & Dana, R. (2021). Autoimmunity in dry eye disease–An updated review of evidence on effector and memory Th17 cells in disease pathogenicity. Autoimmunity Reviews, 20(11), 102933.‏
• Churov, A. V., Mamashov, K. Y., & Novitskaia, A. V. (2020). Homeostasis and the functional roles of CD4+ Treg cells in aging. Immunology Letters, 226, 83-89.‏
• Clayton, J. A. (2018). Dry eye. New England Journal of Medicine, 378(23), 2212-2223.‏
• De Paiva, C. S., Chotikavanich, S., Pangelinan, S. B., Pitcher, J. 3., Fang, B., Zheng, X., ... & Pflugfelder, S. C. (2009). IL-17 disrupts corneal barrier following desiccating stress. Mucosal immunology, 2(3), 243-253.‏
• De Paiva, C. S., Volpe, E. A., Gandhi, N. B., Zhang, X., Zheng, X., Pitcher III, J. D., ... & Pflugfelder, S. C. (2011). Disruption of TGF-β signaling improves ocular surface epithelial disease in experimental autoimmune keratoconjunctivitis sicca. PloS one, 6(12), e29017.‏
• 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, 2486.‏
• Dong, Y., Yang, C., & Pan, F. (2021). Post-translational regulations of Foxp3 in Treg cells and their therapeutic applications. Frontiers in Immunology, 12, 626172.‏
• Donthineni, P. R., Shanbhag, S. S., & Basu, S. (2021, January). An evidence-based strategic approach to prevention and treatment of dry eye disease, a modern global epidemic. In Healthcare (Vol. 9, No. 1, p. 89). MDPI.‏
• Fan, N. W., Dohlman, T. H., Foulsham, W., McSoley, M., Singh, R. B., Chen, Y., & Dana, R. (2021). The role of Th17 immunity in chronic ocular surface disorders. The ocular surface, 19, 157-168.‏
• Fu, R., Jiang, Y., Zhou, J., & Zhang, J. (2019). Rebamipide ophthalmic solution modulates the ratio of T helper cell 17/regulatory T cells in dry eye disease mice. Molecular Medicine Reports, 19(5), 4011-4018.‏
• Ganesalingam, K., Ismail, S., Sherwin, T., & Craig, J. P. (2019). Molecular evidence for the role of inflammation in dry eye disease. Clinical and Experimental Optometry, 102(5), 446-454.‏
• Garcia-Alfaro, P., Garcia, S., Rodriguez, I., & Vergés, C. (2021). Dry eye disease symptoms and quality of life in perimenopausal and postmenopausal women. Climacteric, 24(3), 261-266.‏
• Gomes, J. A., & Santo, R. M. (2019). The impact of dry eye disease treatment on patient satisfaction and quality of life: A review. The Ocular Surface, 17(1), 9-19.‏
• Göschl, L., Scheinecker, C., & Bonelli, M. (2019, May). Treg cells in autoimmunity: from identification to Treg-based therapies. In Seminars in immunopathology (Vol. 41, No. 3, pp. 301-314). Springer Berlin Heidelberg.‏
• Guannan, H., Long, S., Xia, H., Dong, W., & Shaozhen, Z. (2018). Clinical characterisation and cytological study of dry eye in patients with autoimmune disease. J Pak Med Assoc, 68(3), 353-358.‏
• Guo, K., & Zhang, X. (2021). Cytokines that modulate the differentiation of Th17 cells in autoimmune uveitis. Journal of Immunology Research, 2021.‏
• Harrell, C. R., Fellabaum, C., Miloradovic, D., Acovic, A., Miloradovic, D., Markovic, B. S., ... & Volarevic, V. (2021). Therapeutic Potential of „Derived-Multiple Allogeneic Proteins Paracrine Signaling-D-Mapps” in the Treatment of Dry Eye Disease. Serbian Journal of Experimental and Clinical Research.‏
• Hasan, Z. A. (2021). Dry eye syndrome risk factors: A systemic review. Saudi Journal of Ophthalmology, 35(2), 131.‏
• He, X., Liang, B., & Gu, N. (2020). Th17/Treg imbalance and atherosclerosis. Disease Markers, 2020.‏
• Inomata, T., Hua, J., Nakao, T., Shiang, T., Chiang, H., Amouzegar, A., & Dana, R. (2018). Corneal tissue from dry eye donors leads to enhanced graft rejection. Cornea, 37(1), 95.‏
• Kimura, K. (2020). Regulatory T cells in multiple sclerosis. Clinical and Experimental Neuroimmunology, 11(3), 148-155.‏
• Korn, T., & Hiltensperger, M. (2021). Role of IL-6 in the commitment of T cell subsets. Cytokine, 146, 155654.‏
• Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009). IL-17 and Th17 Cells. Annual review of immunology, 27, 485-517.‏
• Krebs, C. F., & Panzer, U. (2018). Plasticity and heterogeneity of Th17 in immune-mediated kidney diseases. Journal of Autoimmunity, 87, 61-68.‏
• Lee, J., Choi, J., Lee, W., Ko, K., & Kim, S. (2015). Dehydrodiconiferyl alcohol (DHCA) modulates the differentiation of Th17 and Th1 cells and suppresses experimental autoimmune encephalomyelitis. Molecular immunology, 68(2), 434-444.‏
• Leonardi, A., Modugno, R. L., & Salami, E. (2021). Allergy and dry eye disease. Ocular immunology and inflammation, 29(6), 1168-1176.‏
• Li, B., Huang, L., Lv, P., Li, X., Liu, G., Chen, Y., ... & Fang, W. (2020). The role of Th17 cells in psoriasis. Immunologic research, 68(5), 296-309.‏
• Li, Y., Li, X., Geng, X., & Zhao, H. (2022). The IL-2A receptor pathway and its role in lymphocyte differentiation and function. Cytokine & Growth Factor Reviews.‏
• Liu, R., Gao, C., Chen, H., Li, Y., Jin, Y., & Qi, H. (2017). Analysis of Th17-associated cytokines and clinical correlations in patients with dry eye disease. PloS one, 12(4), e0173301.‏
• Luckheeram, R. V., Zhou, R., Verma, A. D., & Xia, B. (2012). CD4+ T cells: differentiation and functions. Clinical and developmental immunology, 2012.‏
• Malek, T. R., & Castro, I. (2010). Interleukin-2 receptor signaling: at the interface between tolerance and immunity. Immunity, 33(2), 153-165.‏
• Master, A., Kontzias, A., Huang, L., Huang, W., Tsioulias, A., Zarabi, S., ... & Rigas, B. (2021). The transcriptome of rabbit conjunctiva in dry eye disease: Large-scale changes and similarity to the human dry eye. Plos one, 16(7), e0254036.‏
• Matos, T. R., Hirakawa, M., Alho, A. C., Neleman, L., Graca, L., & Ritz, J. (2021). Maturation and Phenotypic Heterogeneity of Human CD4+ Regulatory T Cells From Birth to Adulthood and After Allogeneic Stem Cell Transplantation. Frontiers in immunology, 11, 570550.‏
• Miao, J., & Zhu, P. (2018). Functional defects of Treg cells: New targets in rheumatic diseases, including ankylosing spondylitis. Current rheumatology reports, 20(5), 1-8.‏
• Miyara, M., & Sakaguchi, S. (2007). Natural regulatory T cells: mechanisms of suppression. Trends in molecular medicine, 13(3), 108-116.‏
• Nicolle, P., Liang, H., Reboussin, E., Rabut, G., Warcoin, E., Brignole-Baudouin, F., ... & Reaux-Le Goazigo, A. (2018). Proinflammatory markers, chemokines, and enkephalin in patients suffering from dry eye disease. International journal of molecular sciences, 19(4), 1221.‏
• Parkin, J., & Cohen, B. (2001). An overview of the immune system. The Lancet, 357(9270), 1777-1789.‏
• Pflugfelder, S. C. (2004). Antiinflammatory therapy for dry eye. American journal of ophthalmology, 137(2), 337-342.‏
• Rao, S. K., Mohan, R., Gokhale, N., Matalia, H., & Mehta, P. (2022). Inflammation and dry eye disease—where are we?. International Journal of Ophthalmology, 15(5), 820.‏
• Rolando, M., & Merayo-Lloves, J. (2022). Management Strategies for Evaporative Dry Eye Disease and Future Perspective. Current Eye Research, 1-11.‏
• Rouen, P. A., & White, M. L. (2018). Dry eye disease: prevalence, assessment, and management. Home healthcare now, 36(2), 74-83.‏
• Scheinecker, C., Göschl, L., & Bonelli, M. (2020). Treg cells in health and autoimmune diseases: new insights from single cell analysis. Journal of autoimmunity, 110, 102376.‏
• Stern, M. E., Schaumburg, C. S., & Pflugfelder, S. C. (2013). Dry eye as a mucosal autoimmune disease. International reviews of immunology, 32(1), 19-41.‏
• Su, Z. J., Yu, X. P., Guo, R. Y., Ming, D. S., Huang, L. Y., Su, M. L., ... & Lin, Z. Z. (2013). Changes in the balance between Treg and Th17 cells in patients with chronic hepatitis B. Diagnostic microbiology and infectious disease, 76(4), 437-444.‏
• Taniki, N., Nakamoto, N., Chu, P. S., Ichikawa, M., Teratani, T., & Kanai, T. (2022, February). Th17 cells in the liver: balancing autoimmunity and pathogen defense. In Seminars in Immunopathology (pp. 1-18). Springer Berlin Heidelberg.‏
• Widjaja-Adhi, M. A. K., Chao, K., & Golczak, M. (2022). Mouse models in studies on the etiology of evaporative dry eye disease. Experimental Eye Research, 109072.‏
• Wu, B., & Wan, Y. (2020). Molecular control of pathogenic Th17 cells in autoimmune diseases. International immunopharmacology, 80, 106187.‏
• Wu, R., Li, N., Zhao, X., Ding, T., Xue, H., Gao, C., ... & Wang, C. (2020). Low-dose Interleukin-2: Biology and therapeutic prospects in rheumatoid arthritis. Autoimmunity Reviews, 19(10), 102645.‏
• Yamaguchi, T. (2018). Inflammatory response in dry eye. Investigative ophthalmology & visual science, 59(14), DES192-DES199.‏
• Yan, J. B., Luo, M. M., Chen, Z. Y., & He, B. H. (2020). The function and role of the Th17/Treg cell balance in inflammatory bowel disease. Journal of Immunology Research, 2020.‏
• Yang, J., Yang, X., Zou, H., & Li, M. (2016). Oxidative stress and Treg and Th17 dysfunction in systemic lupus erythematosus. Oxidative Medicine and Cellular Longevity, 2016.
• Zhang, S., Gang, X., Yang, S., Cui, M., Sun, L., Li, Z., & Wang, G. (2021). The alterations in and the role of the Th17/Treg balance in metabolic diseases. Frontiers in Immunology, 2702.‏
• Zhang, X., Jeyalatha M, V., Qu, Y., He, X., Ou, S., Bu, J., ... & Li, W. (2017). Dry eye management: targeting the ocular surface microenvironment. International journal of molecular sciences, 18(7), 1398.‏
• Zhang, X., Olsen, N., & Zheng, S. G. (2020). The progress and prospect of regulatory T cells in autoimmune diseases. Journal of Autoimmunity, 111, 102461.‏
• Zhu, L., Hua, F., Ding, W., Ding, K., Zhang, Y., & Xu, C. (2020). The correlation between the Th17/Treg cell balance and bone health. Immunity & Ageing, 17(1), 1-10.‏