Endocrinol Metab.  2019 Jun;34(2):132-137. 10.3803/EnM.2019.34.2.132.

Natural Killer Cells and Thyroid Diseases

• Lee EK
• Sunwoo JB

• KMID: 2450512
• DOI: http://doi.org/10.3803/EnM.2019.34.2.132

Abstract

Abnormal production of thyroid hormone is one of the common endocrine disorders, and thyroid hormone production declines with age. The aging process also negatively affects the immune system. An interaction between endocrine system and the immune system has been proposed to be bidirectional. Emerging evidence suggests an interaction between a lymphocyte population, called natural killer (NK) cells and thyroid gland function. Here, we review the relationship between NK cells and thyroid function and disease.

Keyword

Killer cells, natural; Thyroiditis; Thyroid cancer, papillary; Anaplastic; Immunotherapy; Programmed cell death 1

MeSH Terms

Aging
Endocrine System
Immune System
Immunotherapy
Killer Cells, Natural*
Lymphocytes
Thyroid Diseases*
Thyroid Gland*
Thyroiditis

Reference

1. Robertson MJ, Ritz J. Biology and clinical relevance of human natural killer cells. Blood. 1990; 76:2421–2438.

2. Galdiero MR, Varricchi G, Marone G. The immune network in thyroid cancer. Oncoimmunology. 2016; 5:e1168556.

3. Bjorkstrom NK, Ljunggren HG, Michaelsson J. Emerging insights into natural killer cells in human peripheral tissues. Nat Rev Immunol. 2016; 16:310–320.

4. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 2008; 9:503–510.

5. Xu D. Chapter 11, The development and diversity of ILCs, NK cells and their relevance in health and diseases. Regulation of inflammatory signaling in health and disease. Singapore: Springer Singapore;2017. p. 225–244.

6. Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, et al. Innate lymphoid cells: a proposal for uniform nomenclature. Nat Rev Immunol. 2013; 13:145–149.

7. Abel AM, Yang C, Thakar MS, Malarkannan S. Natural killer cells: development, maturation, and clinical utilization. Front Immunol. 2018; 9:1869.

8. Brittenden J, Heys SD, Ross J, Eremin O. Natural killer cells and cancer. Cancer. 1996; 77:1226–1243.

9. Farag SS, VanDeusen JB, Fehniger TA, Caligiuri MA. Biology and clinical impact of human natural killer cells. Int J Hematol. 2003; 78:7–17.

10. Wang F, Tian Z, Wei H. Genomic expression profiling of NK cells in health and disease. Eur J Immunol. 2015; 45:661–678.

11. Horowitz A, Strauss-Albee DM, Leipold M, Kubo J, Nemat-Gorgani N, Dogan OC, et al. Genetic and environmental determinants of human NK cell diversity revealed by mass cytometry. Sci Transl Med. 2013; 5:208ra145.

12. Marquardt N, Beziat V, Nystrom S, Hengst J, Ivarsson MA, Kekalainen E, et al. Cutting edge: identification and characterization of human intrahepatic CD49a+ NK cells. J Immunol. 2015; 194:2467–2471.

13. Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001; 22:633–640.

14. Coutelier JP, Kehrl JH, Bellur SS, Kohn LD, Notkins AL, Prabhakar BS. Binding and functional effects of thyroid stimulating hormone on human immune cells. J Clin Immunol. 1990; 10:204–210.

15. Mocchegiani E, Malavolta M. NK and NKT cell functions in immunosenescence. Aging Cell. 2004; 3:177–184.

16. 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. 2001; 47:282–288.

17. Sharma SD, Tsai V, Proffitt MR. Enhancement of mouse natural killer cell activity by thyroxine. Cell Immunol. 1982; 73:83–97.

18. 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. 1991; 10:226–236.

19. Botella-Carretero JI, Prados A, Manzano L, Montero MT, Escribano L, Sancho J, et al. 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. 2005; 153:223–230.

20. Dorshkind K, Horseman ND. The roles of prolactin, growth hormone, insulin-like growth factor-I, and thyroid hormones in lymphocyte development and function: insights from genetic models of hormone and hormone receptor deficiency. Endocr Rev. 2000; 21:292–312.

21. Provinciali M, Fabris N. Modulation of lymphoid cell sensitivity to interferon by thyroid hormones. J Endocrinol Invest. 1990; 13:187–191.

22. Johansson S, Berg L, Hall H, Hoglund P. NK cells: elusive players in autoimmunity. Trends Immunol. 2005; 26:613–618.

23. Schleinitz N, Vely F, Harle JR, Vivier E. Natural killer cells in human autoimmune diseases. Immunology. 2010; 131:451–458.

24. Pedersen BK, Feldt-Rasmussen U, Bech K, Perrild H, Klarlund K, Hoier-Madsen M. Characterization of the natural killer cell activity in Hashimoto's and Graves' diseases. Allergy. 1989; 44:477–481.

25. Wenzel BE, Chow A, Baur R, Schleusener H, Wall JR. Natural killer cell activity in patients with Graves' disease and Hashimoto's thyroiditis. Thyroid. 1998; 8:1019–1022.

26. 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. 1987; 79:404–408.

27. Hidaka Y, Amino N, Iwatani Y, Kaneda T, Nasu M, Mitsuda N, et al. Increase in peripheral natural killer cell activity in patients with autoimmune thyroid disease. Autoimmunity. 1992; 11:239–246.

28. Hayslip CC, Baker JR Jr, Wartofsky L, Klein TA, Opsahl MS, Burman KD. Natural killer cell activity and serum autoantibodies in women with postpartum thyroiditis. J Clin Endocrinol Metab. 1988; 66:1089–1093.

29. Kuijpens JL, De Hann-Meulman M, Vader HL, Pop VJ, Wiersinga WM, Drexhage HA. Cell-mediated immunity and postpartum thyroid dysfunction: a possibility for the prediction of disease? J Clin Endocrinol Metab. 1998; 83:1959–1966.

30. Cooper DS. Antithyroid drugs. N Engl J Med. 2005; 352:905–917.

31. McGregor AM, Petersen MM, McLachlan SM, Rooke P, Smith BR, Hall R. Carbimazole and the autoimmune response in Graves' disease. N Engl J Med. 1980; 303:302–307.

32. Wang PW, Luo SF, Huang BY, Lin JD, Huang MJ. Depressed natural killer activity in Graves'; disease and during antithyroid medication. Clin Endocrinol (Oxf). 1988; 28:205–214.

33. Mandal A, Viswanathan C. Natural killer cells: in health and disease. Hematol Oncol Stem Cell Ther. 2015; 8:47–55.

34. Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K. Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet. 2000; 356:1795–1799.

35. Haliotis T, Ball JK, Dexter D, Roder JC. Spontaneous and induced primary oncogenesis in natural killer (NK)-cell-deficient beige mutant mice. Int J Cancer. 1985; 35:505–513.

36. Guerra N, Tan YX, Joncker NT, Choy A, Gallardo F, Xiong N, et al. NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy. Immunity. 2008; 28:571–580.

37. Hermanson DL, Kaufman DS. Utilizing chimeric antigen receptors to direct natural killer cell activity. Front Immunol. 2015; 6:195.

38. Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, et al. Innate or adaptive immunity? The example of natural killer cells. Science. 2011; 331:44–49.

39. Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood. 2005; 105:3051–3057.

40. Geller MA, Cooley S, Judson PL, Ghebre R, Carson LF, Argenta PA, et al. A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer. Cytotherapy. 2011; 13:98–107.

41. Romee R, Rosario M, Berrien-Elliott MM, Wagner JA, Jewell BA, Schappe T, et al. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. Sci Transl Med. 2016; 8:357ra123.

42. Fujii R, Jochems C, Tritsch SR, Wong HC, Schlom J, Hodge JW. An IL-15 superagonist/IL-15Rα fusion complex protects and rescues NK cell-cytotoxic function from TGF-β1-mediated immunosuppression. Cancer Immunol Immunother. 2018; 67:675–689.

43. Spolski R, Li P, Leonard WJ. Biology and regulation of IL-2: from molecular mechanisms to human therapy. Nat Rev Immunol. 2018; 18:648–659.

44. Cooper MA, Bush JE, Fehniger TA, VanDeusen JB, Waite RE, Liu Y, et al. In vivo evidence for a dependence on interleukin 15 for survival of natural killer cells. Blood. 2002; 100:3633–3638.

45. Parhar RS, Zou M, Al-Mohanna FA, Baitei EY, Assiri AM, Meyer BF, et al. IL-12 immunotherapy of Braf(V600E)-induced papillary thyroid cancer in a mouse model. Lab Invest. 2016; 96:89–97.

46. Gogali F, Paterakis G, Rassidakis GZ, Kaltsas G, Liakou CI, Gousis P, et al. Phenotypical analysis of lymphocytes with suppressive and regulatory properties (Tregs) and NK cells in the papillary carcinoma of thyroid. J Clin Endocrinol Metab. 2012; 97:1474–1482.

47. Gogali F, Paterakis G, Rassidakis GZ, Liakou CI, Liapi C. CD3(-)CD16(-)CD56(bright) immunoregulatory NK cells are increased in the tumor microenvironment and inversely correlate with advanced stages in patients with papillary thyroid cancer. Thyroid. 2013; 23:1561–1568.

48. Yin M, Di G, Bian M. Dysfunction of natural killer cells mediated by PD-1 and Tim-3 pathway in anaplastic thyroid cancer. Int Immunopharmacol. 2018; 64:333–339.

49. Melillo RM, Guarino V, Avilla E, Galdiero MR, Liotti F, Prevete N, et al. Mast cells have a protumorigenic role in human thyroid cancer. Oncogene. 2010; 29:6203–6215.

50. Wennerberg E, Pfefferle A, Ekblad L, Yoshimoto Y, Kremer V, Kaminskyy VO, et al. Human anaplastic thyroid carcinoma cells are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract NK cells. Clin Cancer Res. 2014; 20:5733–5744.