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While antithyroid drugs, the only available treatment for GD, carry a significant risk of relapse, advances in immunology could pave the way for more effective therapies. Natural killer (NK) cells, divided into cytotoxic CD56dim and cytokine-secreting CD56bright subsets, regulate immune responses through cytokine production and cell lysis and may play a role in the pathogenesis of GD. To investigate their involvement, we conducted flow cytometry on peripheral blood samples from 131 GD patients at various stages (disease onset, on antithyroid drugs, and in remission) and 97 age- and sex-matched healthy controls (HC). We analyzed NK cell subsets, activating (CD16, CD69, NKG2D, NKp30) and inhibitory receptors (CD161, NKG2A), degranulation (CD107a), and intracellular cytokines expression (interferon \u03b3, tumor necrosis factor \u03b1). Statistical comparisons were made between GD patients and HC and across disease stages. GD patients had a higher frequency of total NK cells (p &lt; 0.028) and CD56bright NK cells (p &lt; 0.01) but a lower frequency of CD56dim NK cells (p = 0.005) compared to HC. NK cells in GD patients expressed activating receptors more frequently, except for NKG2D, but had decreased cytokine expression and degranulation ability. At GD onset, patients had higher frequencies of total NK cells, CD56bright NK cells, and NK cells expressing activating receptors compared to patients receiving ATD treatment and those in remission. CD161+ NK cells were lower at GD onset and returned to levels of HC following treatment. Correlation analysis revealed that free thyroxine (FT4) levels were inversely correlated with CD107a+ NK cells (p &lt; 0.05) and positively correlated with CD69+ NK cells (p &lt; 0.01). These findings suggest that hyperthyroidism impairs NK cell degranulation, with the increased frequency of NK cells potentially compensating for their reduced function. This dysfunction may contribute to the unregulated immune response in GD, highlighting NK cells as a potential target for novel therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms26030977","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T04:32:22Z","timestamp":1737693142000},"page":"977","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Natural Killer Cells in Graves\u2019 Disease: Increased Frequency but Impaired Degranulation Ability Compared to Healthy Controls"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1873-3048","authenticated-orcid":false,"given":"Daniela","family":"Gallo","sequence":"first","affiliation":[{"name":"Endocrine Unit, Department of Medicine and Surgery, University of Insubria, ASST Dei Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2360-1621","authenticated-orcid":false,"given":"Eliana","family":"Piantanida","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Medicine and Surgery, University of Insubria, ASST Dei Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Bombelli","sequence":"additional","affiliation":[{"name":"Immunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Lepanto","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Medicine and Surgery, University of Insubria, ASST Dei Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4790-0861","authenticated-orcid":false,"given":"Antonino","family":"Bruno","sequence":"additional","affiliation":[{"name":"Immunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy"},{"name":"Laboratory of Innate Immunity, Unit of Molecular Pathology, Biochemistry, and Immunology, Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Gallazzi","sequence":"additional","affiliation":[{"name":"Laboratory of Innate Immunity, Unit of Molecular Pathology, Biochemistry, and Immunology, Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Bilato","sequence":"additional","affiliation":[{"name":"Immunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy"},{"name":"Laboratory of Innate Immunity, Unit of Molecular Pathology, Biochemistry, and Immunology, Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0723-6424","authenticated-orcid":false,"given":"Marina","family":"Borgese","sequence":"additional","affiliation":[{"name":"Department of Medicine and Technological Innovation, University of Insubria, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denisa","family":"Baci","sequence":"additional","affiliation":[{"name":"Immunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy"},{"name":"Laboratory of Molecular Cardiology Laboratory, IRCCS-Policlinico San Donato, 20097 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4757-7101","authenticated-orcid":false,"given":"Lorenzo","family":"Mortara","sequence":"additional","affiliation":[{"name":"Immunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy"},{"name":"Laboratory of Innate Immunity, Unit of Molecular Pathology, Biochemistry, and Immunology, Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7551-1751","authenticated-orcid":false,"given":"Maria Laura","family":"Tanda","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Medicine and Surgery, University of Insubria, ASST Dei Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101387","DOI":"10.1016\/j.beem.2020.101387","article-title":"Graves\u2019 disease: Epidemiology, genetic and environmental risk factors and viruses","volume":"34","author":"Antonelli","year":"2020","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1080\/17446651.2022.2052044","article-title":"Management of Graves\u2019 hyperthyroidism: Present and future","volume":"17","author":"Bartalena","year":"2022","journal-title":"Expert. Rev. Endocrinol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Davies, T.F., and Latif, R. (2019). Editorial: TSH receptor and autoimmunity. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00019"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/s41574-024-01016-5","article-title":"Graves\u2019 disease: Latest understanding of pathogenesis and treatment options","volume":"20","author":"Lanzolla","year":"2024","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_5","first-page":"1003","article-title":"Antigen-Specific Immunotherapy with Thyrotropin Receptor Peptides in Graves\u2019 Hyperthyroidism: A Phase I Study","volume":"29","author":"Dayan","year":"2024","journal-title":"Thyroid"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1007\/s40618-018-0918-9","article-title":"Antithyroid drug treatment for Graves\u2019 disease: Baseline predictive models of relapse after treatment for a patient-tailored management","volume":"41","author":"Masiello","year":"2018","journal-title":"J. Endocrinol. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/s41577-021-00558-3","article-title":"Natural killer cells in antiviral immunity","volume":"22","author":"Strunz","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/ni1582","article-title":"Functions of natural killer cells","volume":"9","author":"Vivier","year":"2008","journal-title":"Nat. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/s41586-023-06945-1","article-title":"Natural killer cell therapies","volume":"626","author":"Vivier","year":"2024","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/JLB.3MR0820-685R","article-title":"Regulatory functions of NK cells during infections and cancer","volume":"109","author":"Zwirner","year":"2021","journal-title":"J. Leukoc. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kucuksezer, U.C., Aktas Cetin, E., Esen, F., Tahrali, I., Akdeniz, N., Gelmez, M.Y., and Deniz, G. (2021). The Role of Natural Killer Cells in autoimmune diseases. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.622306"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gianchecchi, E., Delfino, D.V., and Fierabracci, A. (2021). Natural Killer Cells: Potential Biomarkers and Therapeutic Target in Autoimmune Diseases?. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.616853"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"965","DOI":"10.4049\/jimmunol.1500591","article-title":"CD56brightCD16- NK Cells Produce Adenosine through a CD38-Mediated Pathway and Act as Regulatory Cells Inhibiting Autologous CD4+ T Cell Proliferation","volume":"195","author":"Morandi","year":"2015","journal-title":"J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1111\/j.1399-0039.2007.00907.x","article-title":"Association of CD94\/NKG2A, CD94\/NKG2C, and its ligand HLA-E polymorphisms with Behcet\u2019s disease","volume":"70","author":"Seo","year":"2007","journal-title":"Tissue Antig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1038\/s41375-024-02271-1","article-title":"PD-1 expression contributes to functional impairment of NK cells in patients with, B-CLL","volume":"38","author":"Farhat","year":"2024","journal-title":"Leukemia"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Gallo, D., Piantanida, E., Gallazzi, M., Bartalena, L., Tanda, M.L., Bruno, A., and Mortara, L. (2020). Immunological drivers in Graves\u2019 disease: NK cells as a master switcher. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00406"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"132","DOI":"10.3803\/EnM.2019.34.2.132","article-title":"Natural Killer Cells and Thyroid Diseases","volume":"34","author":"Lee","year":"2019","journal-title":"Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Gallo, D., Bruno, A., Gallazzi, M., Cattaneo SA, M., Veronesi, G., Genoni, A., Tanda, M.L., Bartalena, L., Passi, A., and Piantanida, E. (2023). Immunomodulatory role of vitamin D and selenium supplementation in newly diagnosed Graves\u2019 disease patients during methimazole treatment. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1145811"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1002\/eji.202049028","article-title":"Human NK cells, their receptors and function","volume":"51","author":"Quatrini","year":"2021","journal-title":"Eur. J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Carrega, P., and Ferlazzo, G. (2012). Natural killer cell distribution and trafficking in human tissues. Front. Immunol., 3.","DOI":"10.3389\/fimmu.2012.00347"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Gallo, D., and Ali, Y. (2023). Editorial: Immunocellular mechanisms and endocrine organs. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1214230"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Terr\u00e9n, I., Orrantia, A., Astarloa-Pando, G., Amarilla-Irusta, A., Zenarruzabeitia, O., and Borrego, F. (2020). Cytokine-Induced Memory-Like NK Cells: From the Basics to Clinical Applications. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.884648"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1111\/j.1365-2567.2010.03360.x","article-title":"Natural killer cells in human autoimmune diseases","volume":"131","author":"Schleinitz","year":"2010","journal-title":"Immunology"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Crinier, A., Narni-Mancinelli, E., Ugolini, S., and Vivier, E. (2020). SnapShot: Natural Killer Cells. Cell, 180.","DOI":"10.1016\/j.cell.2020.02.029"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1158\/2159-8290.CD-20-0655","article-title":"Tumor-Infiltrating Natural Killer Cells","volume":"11","author":"Greppi","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s12016-013-8400-0","article-title":"NK cell trafficking in health and autoimmunity: A comprehensive review","volume":"47","author":"Peng","year":"2014","journal-title":"Clin. Rev. Aller. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cytogfr.2018.08.001","article-title":"Natural killer cells in inflammation and autoimmunity","volume":"42","author":"Zitti","year":"2018","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/imr.13332","article-title":"Tissue-resident memory NK cells: Homing in on local effectors and regulators","volume":"323","author":"Schuster","year":"2024","journal-title":"Immunol. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Fierabracci, A., Delfino, D.V., Markiewicz, M.A., and La Cava, A. (2021). Editorial: The Role of Natural Killer Cells in Autoimmune Diseases. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.786190"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Poggi, A., and Zocchi, M.R. (2014). NK cell autoreactivity and autoimmune diseases. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00027"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s00281-010-0206-z","article-title":"Innate immunity and the pathogenesis of type 1 diabetes","volume":"33","author":"Grieco","year":"2011","journal-title":"Semin. Immunopathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.coi.2009.09.012","article-title":"Natural killer cells in human autoimmunity","volume":"21","author":"Bryceson","year":"2009","journal-title":"Curr. Opin. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Gross, C.C., Schulte-Mecklenbeck, A., Wiendl, H., Marcenaro, E., Kerlero de Rosbo, N., Uccelli, A., and Laroni, A. (2016). Regulatory Functions of Natural Killer Cells in Multiple Sclerosis. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00606"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Siemaszko, J., Marzec-Przyszlak, A., and Bogunia-Kubik, K. (2021). NKG2D Natural Killer Cell Receptor-A Short Description and Potential Clinical Applications. Cells, 10.","DOI":"10.3390\/cells10061420"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Morandi, B., Mortara, L., Chiossone, L., Accolla, R.S., Mingari, M.C., Moretta, L., Moretta, A., and Ferlazzo, G. (2012). Dendritic cell editing by activated natural killer cells results in a more protective cancer-specific immune response. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039170"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Yamin, R., Berhani, O., Peleg, H., Aamar, S., Stein, N., Gamliel, M., Hindi, I., Scheiman-Elazary, A., and Gur, C. (2019). High percentages and activity of synovial fluid NK cells present in patients with advanced stage active Rheumatoid Arthritis. Sci. Rep., 9.","DOI":"10.1038\/s41598-018-37448-z"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1530\/eje.1.01906","article-title":"Defect of a subpopulation of natural killer immune cells in Graves\u2019 disease and Hashimoto\u2019s thyroiditis: Normalizing effect of dehydroepiandrosterone sulfate","volume":"152","author":"Solerte","year":"2005","journal-title":"Eur. J. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Montesinos MD, M., and Pellizas, C.G. (2019). Thyroid Hormone Action on Innate Immunity. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00350"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1089\/thy.2010.0429","article-title":"Thyroid hormones as modulators of immune activities at the cellular level","volume":"21","author":"Incerpi","year":"2011","journal-title":"Thyroid"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.imlet.2017.02.010","article-title":"Modulating the function of the immune system by thyroid hormones and thyrotropin","volume":"184","author":"Jara","year":"2017","journal-title":"Immunol. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kravchenko, V., and Zakharchenko, T. (2023). Thyroid hormones and minerals in immunocorrection of disorders in autoimmune thyroid diseases. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1225494"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ren, X., and Chen, H. (2022). Changes in Th9 and Th17 lymphocytes and functional cytokines and their relationship with thyroid-stimulating hormone receptor antibodies at different stages of Graves\u2019 disease. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.919681"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Morgan, D.J., and Davis, D.M. (2017). Distinct Effects of dexamethasone on human natural killer cell responses dependent on cytokines. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00432"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1016\/j.lfs.2004.07.031","article-title":"Effect of the inhibition of triiodothyronine (T3) production by thiamazole on the T3 and serotonin content of immune cells","volume":"76","author":"Csaba","year":"2005","journal-title":"Life Sci."},{"key":"ref_45","first-page":"617","article-title":"Thyroxine-dependent modulation of natural killer activity","volume":"3","author":"Provinciali","year":"1987","journal-title":"J. Exp. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.4049\/jimmunol.139.7.2502","article-title":"Hyperthyroxinemic mice have reduced natural killer cell activity. Evidence for a defective trigger mechanism","volume":"139","author":"Zakarija","year":"1987","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0960-5428(97)00033-2","article-title":"Immunomodulation of peripheral lymphocytes by hormones of the hypothalamus-pituitary-thyroid axis","volume":"6","author":"Kruger","year":"1996","journal-title":"Adv. Neuroimmunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jim.2004.08.008","article-title":"CD107a as a functional marker for the identification of natural killer cell activity","volume":"294","author":"Alter","year":"2004","journal-title":"J. Immunol. Methods"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.jim.2011.06.002","article-title":"Target-induced natural killer cell loss as a measure of NK cell responses","volume":"370","author":"Warren","year":"2011","journal-title":"J. Immunol. Methods"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Laroni, A., and Uccelli, A. (2020). CD56bright Natural Killer Cells: A Possible Biomarker of Different Treatments in Multiple Sclerosis. J. Clin. 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