Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

The Role of Thyroid Hormone in the Innate and Adaptive Immune Response during Infection

Julia Rubingh, Anne van der Spek, Eric Fliers, Anita Boelen

10.1002/cphy.c200003

Source: Volume 10, Issue 4, September 2020

Published online: September 2020

Full Article on Wiley Online Library



Abstract

In the past decades, there has been growing evidence for a functional interaction between the thyroid hormone and the immune system. This article provides an overview of the mechanisms by which thyroid hormones affect the innate and adaptive immune response during infection.

The influence of thyroid hormone on the most important players of the innate [neutrophils, macrophages, natural killer (NK) cells, and dendritic cells (DCs)] and adaptive immune system (B‐ and T‐lymphocytes) is reviewed here based on both clinical and preclinical studies. The effects of modulation of the immune system by drugs, such as monoclonal antibodies, tyrosine kinase inhibitors, and interferons on thyroid function, are beyond the scope of this article.

Thyroid hormones regulate the activity of neutrophils which is reflected by higher numbers of neutrophils outside the bloodstream and enhanced activity of the respiratory burst following stimulation with thyroid hormone. Hyperthyroidism affects neutrophil function to a larger extent than hypothyroidism. In addition to neutrophil function, macrophage function is strongly affected by thyroid hormones, with triiodothyronine having a pro‐inflammatory effect in these cells. NK cell proliferation and cytotoxic activity are also dependent on thyroid hormone levels. Finally, thyroid hormones enhance DC proliferation and maturation.

In the adaptive immune system, a hyperthyroid state leads to increased activation of lymphocytes. This effect of thyroid hormone is mediated by various factors including NF‐κB and protein kinase C signaling pathways and the β‐adrenergic receptor.

In general, a hyperthyroid state leads to a more activated immune system whereas hypothyroidism leads to a less activated immune system. © 2020 American Physiological Society. Compr Physiol 10:1277‐1287, 2020.

Figure 1. Figure 1. Here the structure of the different thyroid hormones is illustrated. T4 consists of four iodine atoms, whereas T3 only has three iodine atoms, missing one iodine atom on the outer ring.
Figure 2. Figure 2. A schematic overview of the hypothalamus–pituitary–thyroid axis (HTP axis). Thyrotropin‐releasing hormone (TRH) is released by the hypothalamus and stimulates the pituitary gland to release thyroid‐stimulating hormone (TSH). TSH, in turn, stimulates the thyroid gland to produce thyroid hormones T4 and T3. Via a negative feedback loop, T3 and T4 suppress the release of TRH and TSH by the hypothalamus and pituitary gland, respectively.
Figure 3. Figure 3. Cellular thyroid hormone metabolism: The most important thyroid hormone transporters are MCT8 and MCT10, and LAT2. Once in the cytoplasm either deiodinase 3 (D3) transforms T4 into rT3 or deiodinase 1 or 2 (D1 or D2) transform T4 into T3. T3 enters the cell nucleus and binds to a specific region on the DNA, enabling a specific DNA region to be transcribed.
Figure 4. Figure 4. D2 knockdown impairs zebrafish survival during bacterial meningitis. (A) Kaplan–Meier survival curve of zebrafish embryos pretreated with D2 morpholino (D2MO) or scrambled control morpholino (SCMO) during bacterial meningitis induced by injection of 500 CFU of S. pneumoniae into the hindbrain ventricle. (B) Kaplan–Meier survival curve of zebrafish embryos pretreated with D2MO or SCMO or D2MO and T3 during bacterial meningitis. Data represent 40 embryos per group. P‐value for log rank (Mantel‐Cox) test is indicated. Reused, with permission, from van der Spek AH, et al., 2018 84.
Figure 5. Figure 5. NK cell proliferation in the spleen is enhanced by thyroxine. The total number (mean ± SE) of NK cells in the bone marrow and spleen of control (vehicle‐injected; □) and thyroxin‐treated (▪) 6‐month‐old female (A) and male (B) DBA/2 mice. Number of mice is given in parentheses. Reused, with permission, from Mahoney MX, et al., 1998 49.


Figure 1. Here the structure of the different thyroid hormones is illustrated. T4 consists of four iodine atoms, whereas T3 only has three iodine atoms, missing one iodine atom on the outer ring.


Figure 2. A schematic overview of the hypothalamus–pituitary–thyroid axis (HTP axis). Thyrotropin‐releasing hormone (TRH) is released by the hypothalamus and stimulates the pituitary gland to release thyroid‐stimulating hormone (TSH). TSH, in turn, stimulates the thyroid gland to produce thyroid hormones T4 and T3. Via a negative feedback loop, T3 and T4 suppress the release of TRH and TSH by the hypothalamus and pituitary gland, respectively.


Figure 3. Cellular thyroid hormone metabolism: The most important thyroid hormone transporters are MCT8 and MCT10, and LAT2. Once in the cytoplasm either deiodinase 3 (D3) transforms T4 into rT3 or deiodinase 1 or 2 (D1 or D2) transform T4 into T3. T3 enters the cell nucleus and binds to a specific region on the DNA, enabling a specific DNA region to be transcribed.


Figure 4. D2 knockdown impairs zebrafish survival during bacterial meningitis. (A) Kaplan–Meier survival curve of zebrafish embryos pretreated with D2 morpholino (D2MO) or scrambled control morpholino (SCMO) during bacterial meningitis induced by injection of 500 CFU of S. pneumoniae into the hindbrain ventricle. (B) Kaplan–Meier survival curve of zebrafish embryos pretreated with D2MO or SCMO or D2MO and T3 during bacterial meningitis. Data represent 40 embryos per group. P‐value for log rank (Mantel‐Cox) test is indicated. Reused, with permission, from van der Spek AH, et al., 2018 84.


Figure 5. NK cell proliferation in the spleen is enhanced by thyroxine. The total number (mean ± SE) of NK cells in the bone marrow and spleen of control (vehicle‐injected; □) and thyroxin‐treated (▪) 6‐month‐old female (A) and male (B) DBA/2 mice. Number of mice is given in parentheses. Reused, with permission, from Mahoney MX, et al., 1998 49.
References
 1.Alamino VA, Montesinos MDM, Soler MF, Giusiano L, Gigena N, Fozzatti L, Maller SM, Mendez‐Huergo SP, Rabinovich GA, Pellizas CG. Dendritic cells exposed to triiodothyronine deliver pro‐inflammatory signals and amplify IL‐17‐driven immune responses. Cell Physiol Biochem 52: 354‐367, 2019.
 2.Albright JW, Albright JF. Age‐associated decline in natural killer (NK) activity reflects primarily a defect in function of NK cells. Mech Ageing Dev 31: 295‐306, 1985.
 3.Aoyagi K, Takeshige K, Minakami S. Effects of iodothyronines on chemotactic peptide‐receptor binding and superoxide production of human neutrophils. Biochim Biophys Acta 1093: 223‐228, 1991.
 4.Babych H, Antonyak H, Sklyarov AY. The influence of thyroxine on intensity of energy metabolism in bone marrow myeloid cells and neutrophilic polymorphonuclear leukocytes of neonatal pig. Endocr Regul 34: 73‐81, 2000.
 5.Bernal J, Guadano‐Ferraz A, Morte B. Thyroid hormone transporters–Functions and clinical implications. Nat Rev Endocrinol 11: 406‐417, 2015.
 6.Bianco AC, Dumitrescu A, Gereben B, Ribeiro MO, Fonseca TL, Fernandes GW, Bocco B. Paradigms of dynamic control of thyroid hormone signaling. Endocr Rev 40: 1000‐1047, 2019.
 7.Billon C, Canaple L, Fleury S, Deloire A, Beylot M, Dombrowicz D, Del Carmine P, Samarut J, Gauthier K. TRalpha protects against atherosclerosis in male mice: Identification of a novel anti‐inflammatory property for TRalpha in mice. Endocrinology 155: 2735‐2745, 2014.
 8.Bloise FF, Oliveira FL, Nobrega AF, Vasconcellos R, Cordeiro A, Paiva LS, Taub DD, Borojevic R, Pazos‐Moura CC, Mello‐Coelho V. High levels of circulating triiodothyronine induce plasma cell differentiation. J Endocrinol 220: 305‐317, 2014.
 9.Boelen A, Kwakkel J, Wieland CW, St Germain DL, Fliers E, Hernandez A. Impaired bacterial clearance in type 3 deiodinase‐deficient mice infected with Streptococcus pneumoniae. Endocrinology 150: 1984‐1990, 2009.
 10.Botella‐Carretero JI, Prados A, Manzano L, Montero MT, Escribano L, Sancho J, Escobar‐Morreale HF. The effects of thyroid hormones on circulating markers of cell‐mediated immune response, as studied in patients with differentiated thyroid carcinoma before and during thyroxine withdrawal. Eur J Endocrinol 153: 223‐230, 2005.
 11.Boyum A. A one‐stage procedure for isolation of granulocytes and lymphocytes from human blood. General sedimentation properties of white blood cells in a 1g gravity field. Scand J Clin Lab Investig Suppl 97: 51‐76, 1968.
 12.Brent GA. Mechanisms of thyroid hormone action. J Clin Invest 122: 3035‐3043, 2012.
 13.Brodin P, Davis MM. Human immune system variation. Nat Rev Immunol 17: 21‐29, 2017.
 14.Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet 390: 1550‐1562, 2017.
 15.Chaplin DD. Overview of the immune response. J Allergy Clin Immunol 125: S3‐S23, 2010.
 16.Cheng SY. Thyroid hormone receptor mutations and disease: Beyond thyroid hormone resistance. Trends Endocrinol Metab 16: 176‐182, 2005.
 17.Cheng SY, Leonard JL, Davis PJ. Molecular aspects of thyroid hormone actions. Endocr Rev 31: 139‐170, 2010.
 18.Chiamolera MI, Wondisford FE. Minireview: Thyrotropin‐releasing hormone and the thyroid hormone feedback mechanism. Endocrinology 150: 1091‐1096, 2009.
 19.De Leo S, Lee SY, Braverman LE. Hyperthyroidism. Lancet 388: 906‐918, 2016.
 20.De Vito P, Incerpi S, Pedersen JZ, Luly P, Davis FB, Davis PJ. Thyroid hormones as modulators of immune activities at the cellular level. Thyroid 21: 879‐890, 2011.
 21.Dedecjus M, Stasiolek M, Brzezinski J, Selmaj K, Lewinski A. Thyroid hormones influence human dendritic cells' phenotype, function, and subsets distribution. Thyroid 21: 533‐540, 2011.
 22.Fernandez V, Videla LA. On the mechanism of thyroid hormone‐induced respiratory burst activity in rat polymorphonuclear leukocytes. Free Radic Biol Med 19: 359‐363, 1995.
 23.Forner MA, Barriga C, Ortega E. Exercise‐induced stimulation of murine macrophage phagocytosis may be mediated by thyroxine. J Appl Physiol (1985) 80: 899‐903, 1996.
 24.Foster MP, Montecino‐Rodriguez E, Dorshkind K. Proliferation of bone marrow pro‐B cells is dependent on stimulation by the pituitary/thyroid axis. J Immunol 163: 5883‐5890, 1999.
 25.Frick LR, Rapanelli M, Bussmann UA, Klecha AJ, Arcos ML, Genaro AM, Cremaschi GA. Involvement of thyroid hormones in the alterations of T‐cell immunity and tumor progression induced by chronic stress. Biol Psychiatry 65: 935‐942, 2009.
 26.Friesema EC, Jansen J, Jachtenberg JW, Visser WE, Kester MH, Visser TJ. Effective cellular uptake and efflux of thyroid hormone by human monocarboxylate transporter 10. Mol Endocrinol 22: 1357‐1369, 2008.
 27.Furuya F, Ishii T, Tamura S, Takahashi K, Kobayashi H, Ichijo M, Takizawa S, Kaneshige M, Suzuki‐Inoue K, Kitamura K. The ligand‐bound thyroid hormone receptor in macrophages ameliorates kidney injury via inhibition of nuclear factor‐kappaB activities. Sci Rep 7: 43960, 2017.
 28.Gigena N, Alamino VA, Montesinos MD, Nazar M, Louzada RA, Wajner SM, Maia AL, Masini‐Repiso AM, Carvalho DP, Cremaschi GA, Pellizas CG. Dissecting thyroid hormone transport and metabolism in dendritic cells. J Endocrinol 232: 337‐350, 2017.
 29.Haddad EE, Mashaly MM. Chicken growth hormone, triiodothyronine and thyrotropin releasing hormone modulation of the levels of chicken natural cell‐mediated cytotoxicity. Dev Comp Immunol 15: 65‐71, 1991.
 30.Haddad EE, Mashaly MM. In vivo effects of TRH, T3 and cGH on antibody production and T‐ and B‐lymphocytes proliferation in immature male chickens. Immunol Investig 20: 557‐568, 1991.
 31.Harris AR, Christianson D, Smith MS, Fang SL, Braverman LE, Vagenakis AG. The physiological role of thyrotropin‐releasing hormone in the regulation of thyroid‐stimulating hormone and prolactin secretion in the rat. J Clin Invest 61: 441‐448, 1978.
 32.Hastings ML, Milcarek C, Martincic K, Peterson ML, Munroe SH. Expression of the thyroid hormone receptor gene, erbAalpha, in B lymphocytes: Alternative mRNA processing is independent of differentiation but correlates with antisense RNA levels. Nucleic Acids Res 25: 4296‐4300, 1997.
 33.Hones GS, Rakov H, Logan J, Liao XH, Werbenko E, Pollard AS, Praestholm SM, Siersbaek MS, Rijntjes E, Gassen J, Latteyer S, Engels K, Strucksberg KH, Kleinbongard P, Zwanziger D, Rozman J, Gailus‐Durner V, Fuchs H, Hrabe de Angelis M, Klein‐Hitpass L, Kohrle J, Armstrong DL, Grontved L, Bassett JHD, Williams GR, Refetoff S, Fuhrer D, Moeller LC. Noncanonical thyroid hormone signaling mediates cardiometabolic effects in vivo. Proc Natl Acad Sci U S A 114: E11323‐E11332, 2017.
 34.Hu W, Wang G, Huang D, Sui M, Xu Y. Cancer immunotherapy based on natural killer cells: Current progress and new opportunities. Front Immunol 10: 1205, 2019.
 35.Huffman LJ, Beighley CM, Frazer DG, McKinney WG, Porter DW. Increased susceptibility of the lungs of hyperthyroid rats to oxidant injury: Specificity of effects. Toxicology 225: 119‐127, 2006.
 36.Huffman LJ, Judy DJ, Brumbaugh K, Frazer DG, Reynolds JS, McKinney WG, Goldsmith WT. Hyperthyroidism increases the risk of ozone‐induced lung toxicity in rats. Toxicol Appl Pharmacol 173: 18‐26, 2001.
 37.Ingram KG, Crouch DA, Douez DL, Croy BA, Woodward B. Effects of triiodothyronine supplements on splenic natural killer cells in malnourished weanling mice. Int J Immunopharmacol 17: 21‐32, 1995.
 38.Iwasaki A, Medzhitov R. Control of adaptive immunity by the innate immune system. Nat Immunol 16: 343‐353, 2015.
 39.Jafarzadeh A, Poorgholami M, Izadi N, Nemati M, Rezayati M. Immunological and hematological changes in patients with hyperthyroidism or hypothyroidism. Clin Invest Med 33: E271‐E279, 2010.
 40.Karanikas G, John P, Wahl K, Schuetz M, Dudczak R, Willheim M. T‐lymphocyte cytokine production patterns in nonimmune severe hypothyroid state and after thyroid hormone replacement therapy. Thyroid 14: 488‐492, 2004.
 41.Kersseboom S, Visser TJ. Tissue‐specific effects of mutations in the thyroid hormone transporter MCT8. Arq Bras Endocrinol Metabol 55: 1‐5, 2011.
 42.Klecha AJ, Barreiro Arcos ML, Genaro AM, Gorelik G, Silberman DM, Caro R, Cremaschi GA. Different mitogen‐mediated Beta‐adrenergic receptor modulation in murine T lymphocytes depending on the thyroid status. Neuroimmunomodulation 12: 92‐99, 2005.
 43.Klecha AJ, Genaro AM, Gorelik G, Barreiro Arcos ML, Silberman DM, Schuman M, Garcia SI, Pirola C, Cremaschi GA. Integrative study of hypothalamus‐pituitary‐thyroid‐immune system interaction: Thyroid hormone‐mediated modulation of lymphocyte activity through the protein kinase C signaling pathway. J Endocrinol 189: 45‐55, 2006.
 44.Kmiec Z, Mysliwska J, Rachon D, Kotlarz G, Sworczak K, Mysliwski A. Natural killer activity and thyroid hormone levels in young and elderly persons. Gerontology 47: 282‐288, 2001.
 45.Kwakkel J, Surovtseva OV, de Vries EM, Stap J, Fliers E, Boelen A. A novel role for the thyroid hormone‐activating enzyme type 2 deiodinase in the inflammatory response of macrophages. Endocrinology 155: 2725‐2734, 2014.
 46.Leon B, Ballesteros‐Tato A, Lund FE. Dendritic cells and B cells: Unexpected partners in Th2 development. J Immunol 193: 1531‐1537, 2014.
 47.Ley K, Hoffman HM, Kubes P, Cassatella MA, Zychlinsky A, Hedrick CC, Catz SD. Neutrophils: New insights and open questions. Sci Immunol 3: eaat4579, 2018.
 48.Magsino CH Jr, Hamouda W, Ghanim H, Browne R, Aljada A, Dandona P. Effect of triiodothyronine on reactive oxygen species generation by leukocytes, indices of oxidative damage, and antioxidant reserve. Metabolism 49: 799‐803, 2000.
 49.Mahoney MX, Currier NL, Miller SC. Natural killer cell levels in older adult mice are gender‐dependent: Thyroxin is a gender‐independent natural killer cell stimulant. Nat Immun 16: 165‐174, 1998.
 50.Mancini A, Di Segni C, Raimondo S, Olivieri G, Silvestrini A, Meucci E, Curro D. Thyroid hormones, oxidative stress, and inflammation. Mediat Inflamm 2016: 6757154, 2016.
 51.Marino F, Guasti L, Cosentino M, De Piazza D, Simoni C, Piantanida E, Cimpanelli M, Klersy C, Bartalena L, Venco A, Lecchini S. Thyroid hormone regulation of cell migration and oxidative metabolism in polymorphonuclear leukocytes: Clinical evidence in thyroidectomized subjects on thyroxine replacement therapy. Life Sci 78: 1071‐1077, 2006.
 52.Mascanfroni ID, Montesinos Mdel M, Alamino VA, Susperreguy S, Nicola JP, Ilarregui JM, Masini‐Repiso AM, Rabinovich GA, Pellizas CG. Nuclear factor (NF)‐kappaB‐dependent thyroid hormone receptor beta1 expression controls dendritic cell function via Akt signaling. J Biol Chem 285: 9569‐9582, 2010.
 53.Mezosi E, Szabo J, Nagy EV, Borbely A, Varga E, Paragh G, Varga Z. Nongenomic effect of thyroid hormone on free‐radical production in human polymorphonuclear leukocytes. J Endocrinol 185: 121‐129, 2005.
 54.Mihara S, Suzuki N, Wakisaka S, Suzuki S, Sekita N, Yamamoto S, Saito N, Hoshino T, Sakane T. Effects of thyroid hormones on apoptotic cell death of human lymphocytes. J Clin Endocrinol Metab 84: 1378‐1385, 1999.
 55.Miller RA. The aging immune system: Primer and prospectus. Science 273: 70‐74, 1996.
 56.Montecino‐Rodriguez E, Clark R, Johnson A, Collins L, Dorshkind K. Defective B cell development in Snell dwarf (dw/dw) mice can be corrected by thyroxine treatment. J Immunol 157: 3334‐3340, 1996.
 57.Montesinos MDM, Pellizas CG. Thyroid hormone action on innate immunity. Front Endocrinol (Lausanne) 10: 350, 2019.
 58.Mooij P, Simons PJ, de Haan‐Meulman M, de Wit HJ, Drexhage HA. Effect of thyroid hormones and other iodinated compounds on the transition of monocytes into veiled/dendritic cells: Role of granulocyte‐macrophage colony‐stimulating factor, tumour‐necrosis factor‐alpha and interleukin‐6. J Endocrinol 140: 503‐512, 1994.
 59.Mullur R, Liu YY, Brent GA. Thyroid hormone regulation of metabolism. Physiol Rev 94: 355‐382, 2014.
 60.Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 11: 723‐737, 2011.
 61.Nakanishi K, Taniguchi Y, Onji M. Triiodothyronine enhances expression of the interleukin‐2 receptor alpha chain. Endocr J 46: 437‐442, 1999.
 62.Nandakumar DN, Koner BC, Vinayagamoorthi R, Nanda N, Negi VS, Goswami K, Bobby Z, Hamide A. Activation of NF‐kappaB in lymphocytes and increase in serum immunoglobulin in hyperthyroidism: Possible role of oxidative stress. Immunobiology 213: 409‐415, 2008.
 63.Nicholson LB. The immune system. Essays Biochem 60: 275‐301, 2016.
 64.Ning Y, Zhang M, Du YH, Zhang HN, Li LY, Qin YW, Wen WW, Zhao QM. Effects of thyroid hormone on macrophage dysfunction induced by oxidized low‐density lipoprotein. Sheng Li Xue Bao 70: 141‐148, 2018.
 65.Ortega E, Forner MA, Garcia JJ, Rodriguez AB, Barriga C. Enhanced chemotaxis of macrophages by strenuous exercise in trained mice: Thyroid hormones as possible mediators. Mol Cell Biochem 201: 41‐47, 1999.
 66.Ortiga‐Carvalho TM, Chiamolera MI, Pazos‐Moura CC, Wondisford FE. Hypothalamus‐pituitary‐thyroid axis. Compr Physiol 6: 1387‐1428, 2016.
 67.Pacini F, Nakamura H, DeGroot LJ. Effect of hypo‐ and hyperthyroidism on the balance between helper and suppressor T cells in rats. Acta Endocrinol 103: 528‐534, 1983.
 68.Papic M, Stein‐Streilein J, Zakarija M, McKenzie JM, Guffee J, Fletcher MA. Suppression of peripheral blood natural killer cell activity by excess thyroid hormone. J Clin Invest 79: 404‐408, 1987.
 69.Peeters RP, Visser TJ. Metabolism of thyroid hormone. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, Dungan K, Grossman A, Hershman JM, Kaltsas G, Koch C, Kopp P, Korbonits M, McLachlan R, Morley JE, New M, Perreault L, Purnell J, Rebar R, Singer F, Trence DL, Vinik A, Wilson DP, editors. Endotext. South Dartmouth, MA, 2000.
 70.Provinciali M, Di Stefano G, Fabris N. Regulation of NK cell lymphokine responsiveness by pituitary‐thyroid hormones during ontogeny in mice. Suggestion for a sequential neuroendocrine‐immune cross‐talk. Ann N Y Acad Sci 741: 73‐80, 1994.
 71.Provinciali M, Muzzioli M, Di Stefano G, Fabris N. Recovery of spleen cell natural killer activity by thyroid hormone treatment in old mice. Nat Immun Cell Growth Regul 10: 226‐236, 1991.
 72.Robinson MV, Obut TA, Mel'nikova EV, Trufakin VA. Effects of thyroxin and mercazolyl on immunological parameters of blood lymphocytes and lymphoid organs. Bull Exp Biol Med 156: 236‐238, 2013.
 73.Robinson MV, Obut TA, Melnikova EV, Trufakin VA. Parameters of cellular and humoral immunity in experimental hyperthyroidism and its correction. Bull Exp Biol Med 156: 473‐475, 2014.
 74.Satpathy AT, Wu X, Albring JC, Murphy KM. Re(de)fining the dendritic cell lineage. Nat Immunol 13: 1145‐1154, 2012.
 75.Sharma SD, Tsai V, Proffitt MR. Enhancement of mouse natural killer cell activity by thyroxine. Cell Immunol 73: 83‐97, 1982.
 76.Shi C, Pamer EG. Monocyte recruitment during infection and inflammation. Nat Rev Immunol 11: 762‐774, 2011.
 77.Szabo J, Foris G, Mezosi E, Nagy EV, Paragh G, Sztojka I, Leovey A. Parameters of respiratory burst and arachidonic acid metabolism in polymorphonuclear granulocytes from patients with various thyroid diseases. Exp Clin Endocr Diab 104: 172‐176, 1996.
 78.Taylor PN, Peeters R, Dayan CM. Genetic abnormalities in thyroid hormone deiodinases. Curr Opin Endocrinol Diabetes Obes 22: 402‐406, 2015.
 79.van der Spek AH, Bloise FF, Tigchelaar W, Dentice M, Salvatore D, van der Wel NN, Fliers E, Boelen A. The thyroid hormone inactivating enzyme type 3 deiodinase is present in bactericidal granules and the cytoplasm of human neutrophils. Endocrinology 157: 3293‐3305, 2016.
 80.van der Spek AH, Fliers E, Boelen A. The classic pathways of thyroid hormone metabolism. Mol Cell Endocrinol 458: 29‐38, 2017.
 81.van der Spek AH, Fliers E, Boelen A. Thyroid hormone metabolism in innate immune cells. J Endocrinol 232: R67‐R81, 2017.
 82.van der Spek AH, Jim KK, Karaczyn A, van Beeren HC, Ackermans MT, Darras VM, Vandenbroucke‐Grauls C, Hernandez A, Brouwer MC, Fliers E, van de Beek D, Boelen A. The thyroid hormone inactivating type 3 deiodinase is essential for optimal neutrophil function: Observations from three species. Endocrinology 159: 826‐835, 2018.
 83.van der Spek AH, Surovtseva OV, Aan S, Tool ATJ, van de Geer A, Demir K, van Gucht ALM, van Trotsenburg ASP, van den Berg TK, Fliers E, Boelen A. Increased circulating interleukin‐8 in patients with resistance to thyroid hormone receptor alpha. Endocr Connect 6: 731‐740, 2017.
 84.van der Spek AH, Surovtseva OV, Jim KK, van Oudenaren A, Brouwer MC, Vandenbroucke‐Grauls C, Leenen PJM, van de Beek D, Hernandez A, Fliers E, Boelen A. Regulation of intracellular triiodothyronine is essential for optimal macrophage function. Endocrinology 159: 2241‐2252, 2018.
 85.van Gucht AL, Meima ME, Zwaveling‐Soonawala N, Visser WE, Fliers E, Wennink JM, Henny C, Visser TJ, Peeters RP, van Trotsenburg AS. Resistance to thyroid hormone alpha in an 18‐month‐old girl: Clinical, therapeutic, and molecular characteristics. Thyroid 26: 338‐346, 2016.
 86.Varedi M, Shiri H, Moattari A, Omrani GH, Amirghofran Z. Hyperthyroid state or in vitro thyroxine treatment modulates TH1/TH2 responses during exposure to HSV‐1 antigens. J Immunotoxicol 11: 160‐165, 2014.
 87.Vinayagamoorthi R, Koner BC, Kavitha S, Nandakumar DN, Padma Priya P, Goswami K. Potentiation of humoral immune response and activation of NF‐kappaB pathway in lymphocytes in experimentally induced hyperthyroid rats. Cell Immunol 238: 56‐60, 2005.
 88.Visser TJ. Cellular uptake of thyroid hormones. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, Dungan K, Grossman A, Hershman JM, Kaltsas G, Koch C, Kopp P, Korbonits M, McLachlan R, Morley JE, New M, Perreault L, Purnell J, Rebar R, Singer F, Trence DL, Vinik A, Wilson DP, editors. Endotext. South Dartmouth, MA, 2000.
 89.Visser WE, Friesema EC, Visser TJ. Minireview: Thyroid hormone transporters: The knowns and the unknowns. Mol Endocrinol 25: 1‐14, 2011.
 90.Wang J, Klein JR. Hormone regulation of murine T cells: Potent tissue‐specific immunosuppressive effects of thyroxine targeted to gut T cells. Int Immunol 8: 231‐235, 1996.
 91.Yao C, Zhang J, Wang L, Guo Y, Tian Z. Inhibitory effects of thyroxine on cytokine production by T cells in mice. Int Immunopharmacol 7: 1747‐1754, 2007.
 92.Yatim KM, Lakkis FG. A brief journey through the immune system. Clin J Am Soc Nephrol 10: 1274‐1281, 2015.
 93.Yu G, Tzouvelekis A, Wang R, Herazo‐Maya JD, Ibarra GH, Srivastava A, de Castro JPW, DeIuliis G, Ahangari F, Woolard T, Aurelien N, Arrojo EDR, Gan Y, Graham M, Liu X, Homer RJ, Scanlan TS, Mannam P, Lee PJ, Herzog EL, Bianco AC, Kaminski N. Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function. Nat Med 24: 39‐49, 2018.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: The Role of Thyroid Hormone in the Innate and Adaptive Immune Response during Infection
 

How to Cite

Julia Rubingh, Anne van der Spek, Eric Fliers, Anita Boelen. The Role of Thyroid Hormone in the Innate and Adaptive Immune Response during Infection. Compr Physiol 2020, 10: 1277-1287. doi: 10.1002/cphy.c200003