Th17 Cells: The Silent Architects of Hashimoto’s Thyroiditis

Netra Agarwal, Savitran Eshwar, Sharon Philip Jain, Anuj Pandey, Apurva Abitkar

Abstract


Hashimoto’s Thyroiditis (HT) is a chronic condition where the immune system attacks the thyroid gland. A life-long persisting autoimmune condition that begins with inflammation leading to thyroid dysfunction. Our research focuses on the pivotal part of the process: T helper 17 (Th17) cells since HT usually focuses on the other immune cells. Our study reveals that Th17 and the cytokine IL-17 are responsible for the condition’s inflammatory cascade. Th17 cells become proactive, leading to excessive inflammation, which ultimately causes thyroid tissue damage in HT. These cells are pro-inflammatory as they produce IL-17, which recruits other immune cells and exacerbates tissue destruction. This balance between the Th-17 and the regulatory Treg or T cells normally responsible for keeping immune response in check gets disrupted in HT, causing a persistent attack on the immune system. Our findings in this paper highlight the importance of targeting the Th-17 and IL-17 pathways as a potential therapeutic strategy. When we shift our focus on these, we may be able to develop treatments that help manage the inflammation and prevent thyroid damage.


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Berry SD, Dossou C, Kashif A, Sharifinejad N, Azizi G, Hamedifar H, Sabzvari A, Zian Z. The role of IL-17 and anti-IL-17 agents in the immunopathogenesis and management of autoimmune and inflammatory diseases. International immunopharmacology. 2022 Jan 1;102:108402.

Kebir H, Kreymborg K, Ifergan I, Dodelet-Devillers A, Cayrol R, Bernard M, Giuliani F, Arbour N, Becher B, Prat A. Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nature medicine. 2007 Oct;13(10):1173-5.

Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006 Sep 22;126(6):1121-33.

Ragusa F, Fallahi P, Elia G, Gonnella D, Paparo SR, Giusti C, Churilov LP, Ferrari SM, Antonelli A. Hashimotos’ thyroiditis: Epidemiology, pathogenesis, clinic and therapy. Best Practice & Research Clinical Endocrinology & Metabolism. 2019 Dec 1;33(6):101367.

Wrońska K, Hałasa M, Szczuko M. The Role of the Immune System in the Course of Hashimoto’s Thyroiditis: The Current State of Knowledge. International Journal of Molecular Sciences. 2024 Jan 1;25(13):6883.

Luty J, Ruckemann-Dziurdzińska K, Witkowski JM, Bryl E. Immunological aspects of autoimmune thyroid disease – Complex interplay between cells and cytokines. Cytokine. 2019 Apr;116:128–33.

Dong C. Cytokine Regulation and Function in T Cells. Annual Review of Immunology. 2021 Apr 26;39:51–76.

Yasuda K, Takeuchi Y, Hirota K. The pathogenicity of Th17 cells in autoimmune diseases. Seminars in Immunopathology. 2019 Mar 19;41(3):283–97.

Aghbash PS, Hemmat N, Nahand JS, Shamekh A, Memar MY, Babaei A, et al. The role of Th17 cells in viral infections. International Immunopharmacology. 2021 Feb 1;91:107331.

Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. The Journal of Experimental Medicine. 2005 Jan 17;201(2):233–40.

Naguib R. Potential relationships between COVID-19 and the thyroid gland: an update. Journal of International Medical Research. 2022 Feb;50(2):030006052210828.

Lee Y, Kuchroo V. Defining the functional states of Th17 cells. F1000Research. 2015 May 28;4:132.

Janegova A, Janega P, Rychly B, Kuracinova K, Babal P. Rola infekcji wirusem Epstein-Barr’a w rozwoju autoimmunologicznych chorób tarczycy. Endokrynologia Polska. 2015 May 1;66(2):132–6.

Shukla SK, Singh G, Ahmad S, Pant P. Infections, genetic and environmental factors in pathogenesis of autoimmune thyroid diseases. Microbial Pathogenesis. 2018 Mar;116:279–88.

Smatti MK, Cyprian FS, Nasrallah GK, Al Thani AA, Almishal RO, Yassine HM. Viruses and Autoimmunity: a Review on the Potential Interaction and Molecular Mechanisms. Viruses. 2019 Aug 19;11(8):762.

Liu Y, Tang X, Tian J, Zhu C, Peng H, Rui K, et al. Th17/Treg Cells Imbalance and GITRL Profile in Patients with Hashimoto’s Thyroiditis. International Journal of Molecular Sciences. 2014 Nov 25;15(12):21674–86.

Liu Y, Cui X, Wang S, Liu J, Zhao N, Huang M, et al. Elevated MicroRNA-326 Levels Regulate the IL-23/IL-23R/Th17 Cell Axis in Hashimoto’s Thyroiditis by Targeting a Disintegrin and Metalloprotease 17. Thyroid. 2020 Sep 1;30(9):1327–37.

Zheng T, Xu C, Mao C, Mou X, Wu F, Wang X, et al. Increased Interleukin-23 in Hashimoto’s Thyroiditis Disease Induces Autophagy Suppression and Reactive Oxygen Species Accumulation. Frontiers in Immunology. 2018 Jan 29;9.

Nodehi M, Ajami A, Izad M, Asgarian Omran H, Chahardoli R, Amouzegar A, et al. Effects of vitamin D supplements on frequency of CD4+ T-cell subsets in women with Hashimoto’s thyroiditis: a double-blind placebo-controlled study. European Journal of Clinical Nutrition. 2019 Jan 29;73(9):1236–43.

Ma X, Wang M, Xu F, Hao S. The Imbalance in Th17 and Treg Cells in Polycystic Ovarian Syndrome Patients with Autoimmune Thyroiditis. Immunological Investigations. 2021 Apr 26;1–12.

Fang J, Yu L, Zhuang LG, Pei XY, Wang Q, Jin GX. The changes in peripheral blood Th17 and Treg ratios in Hashimoto’s thyroiditis are accompanied by differential PD-1/PD-L1 expression. Frontiers in Endocrinology. 2022 Aug 25;13.

Li D, Cai W, Gu R, Zhang Y, Zhang H, Tang K, et al. Th17 cell plays a role in the pathogenesis of Hashimoto’s thyroiditis in patients. Clinical Immunology. 2013 Dec 1;149(3):411–20.

Han LT, Hu JQ, Ma B, Wen D, Zhang TT, Lu ZW, et al. IL-17A increases MHC class I expression and promotes T cell activation in papillary thyroid cancer patients with coexistent Hashimoto’s thyroiditis. Diagnostic Pathology. 2019 Jun 4;14(1).

Akbay EA, Koyama S, Liu Y, Dries R, Bufe LE, Silkes M, Alam MM, Magee DM, Jones R, Jinushi M, Kulkarni M. Interleukin-17A promotes lung tumor progression through neutrophil attraction to tumor sites and mediating resistance to PD-1 blockade. Journal of thoracic oncology. 2017 Aug 1;12(8):1268-79.

Bliddal S, Borresen SW, Feldt-Rasmussen U. Thyroid Autoimmunity and Function after Treatment with Biological Antirheumatic Agents in Rheumatoid Arthritis. Frontiers in Endocrinology. 2017 Jul 31;8.

Bunte K, Beikler T. Th17 Cells and the IL-23/IL-17 Axis in the Pathogenesis of Periodontitis and Immune-Mediated Inflammatory Diseases. International journal of molecular sciences. 2019;20(14):3394.

Waliszewska-Prosół M, Ejma M. Hashimoto Encephalopathy—Still More Questions than Answers. Cells. 2022 Sep 14;11(18):2873.

Wang J, Wang C, Liu L, Hong S, Ru Y, Sun X, et al. Adverse events associated with anti-IL-17 agents for psoriasis and psoriatic arthritis: a systematic scoping review. Frontiers in Immunology. 2023 Jan 31;14.

Tywanek E, Michalak A, Świrska J, Zwolak A. Autoimmunity, New Potential Biomarkers and the Thyroid Gland—The Perspective of Hashimoto’s Thyroiditis and Its Treatment. International Journal of Molecular Sciences. 2024 Jan 1;25(9):4703.

Caturegli P, De Remigis A, Rose NR. Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev. 2014;13(4-5):391-7.

Messina F, Piaserico S. The dark side of the moon: the immune-mediated adverse events of IL-17A/IL-17R inhibition. The Journal of Dermatological Treatment. 2022 Aug 1 [cited 2023 Mar 28];33(5):2443–54.

Țiburcă L, Bembea M, Zaha DC, Jurca AD, Vesa CM, Rațiu IA, et al. The Treatment with Interleukin 17 Inhibitors and Immune-Mediated Inflammatory Diseases. Current Issues in Molecular Biology. 2022 Apr 26;44(5):1851–66.

McGeachy MJ, Cua DJ, Gaffen SL. The IL-17 family of cytokines in health and disease. Immunity. 2019 Apr 16;50(4):892-906.

Geren

ova J, Wolff ASB, Nygaard B, Karlsen AE, Kamhieh-Milz J, Kjellman P, et al. IL-12p70-producing dendritic cells and T helper 17 cells in autoimmune thyroid disease: differences in Hashimoto’s thyroiditis and Graves’ disease. Scand J Immunol. 2019;90(2):e12777.

Marazuela M, Sanchez-Madrid F. Circulating blood T follicular helper cells in autoimmune thyroid diseases: Differences in Hashimoto thyroiditis and Graves’ disease. J Clin Endocrinol Metab. 2018;103(10):3663–72.

Heward JM, Gough SC. Genetic susceptibility to the development of autoimmune disease. Clin Sci (Lond). 1997;93(6):479–91.

Gershwin ME, Cohen IR, editors. Infection and autoimmunity. Elsevier; 2019 Aug 27.

Casella G, D’Incà R, Olivieri O, Scapini P, Zanotti R, Zorzi F, et al. Stratifying risks of anti-TNF-α therapy for perianal Crohn’s disease. World Journal of Gastroenterology. 2022 Apr 14;28(14):1532–53.

Brown MA, Kennedy LG, MacGregor AJ, Darke C, Duncan E, Shatford JL, et al. Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology. 1997 Sep;40(9):1823-8.




DOI: http://dx.doi.org/10.52155/ijpsat.v46.1.6523

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