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Silica-Induced Immunotoxicity: Chronic and Aberrant Activation of Immune Cells

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Allergy and Immunotoxicology in Occupational Health

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Abstract

Occupational and chronic exposure to silica particles causes pulmonary fibrosis known as silicosis, which is a typical form of pneumoconiosis. Although the respiratory complications of silicosis include pulmonary tuberculosis, pleurisy, bronchitis, and other disorders such as lung cancer, silicosis (SIL) patients often suffer from complications of autoimmune diseases such as rheumatoid arthritis (RA), systemic sclerosis (SSc), and other forms of these conditions. The mechanisms causing impairment of immunity by silica exposure were considered adjuvant effects of these particles, and we have been investigating the direct effects of particles on immune cells, particularly T cells, and found chronic activation of both responder and regulatory T helper cells. The results of chronic activation indicated that responder T cells obtain resistance against CD95/Fas-mediated apoptosis to survive longer, whereas regulatory T cells become prone to CD95/Fas-mediated apoptosis and die quickly. These findings suggest that the imbalance of these cells may initiate the observed autoimmune disorders. Furthermore, various autoantibodies were detected in the serum of SIL without any symptoms of autoimmune diseases. Further investigation is needed to study the effects of silica on other immune cell types such as Th17, dendritic, and B cells. Adequate preventive tools against the progression of immunological impairments are also required to improve occupational health.

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References

  1. Weill H, Jones RN, Raymond Parkes W. Silicosis and related diseases. In: Raymond Parkes W, editor. Occupational lung disorders. 3rd ed. Oxford: Butterworth-Heinemann Ltd; 1994. p. 285–339.

    Google Scholar 

  2. Weissman DN, Banks DE. Silicosis. In: Schwarz MI, King Jr TE, editors. Interstitial lung disease. 4th ed. Hamilton: BC Decker; 2003. p. 387–401.

    Google Scholar 

  3. Kelley J. Occupational lung diseases caused by asbestos, silica, and other silicates. In: Baum GL, Crapo JD, Celli BR, Karlinsky JB, editors. Textbook of pulmonary diseases, vol. 1. 6th ed. Philadelphia: Lippincott-Raven Publishers; 1998. p. 659–82.

    Google Scholar 

  4. Cullinan P, Reid P. Pneumoconiosis. Prim Care Respir J. 2013;22(2):249–52. doi:10.4104/pcrj.2013.00055.

    Article  PubMed  Google Scholar 

  5. Leung CC, Yu IT, Chen W. Silicosis. Lancet. 2012;379(9830):2008–18. doi:10.1016/S0140-6736(12)60235-9.

    Article  CAS  PubMed  Google Scholar 

  6. Rees D, Murray J. Silica, silicosis and tuberculosis. Int J Tuberc Lung Dis. 2007;11(5):474–84.

    CAS  PubMed  Google Scholar 

  7. Silica, some silicates, coal dust and para-aramid fibrils. In: IARC monographs on the evaluation of carcinogenic risks to humans. Volume 68. Lyon: WHO Press. 1997.

    Google Scholar 

  8. Steenland K, Ward E. Silica: a lung carcinogen. CA Cancer J Clin. 2014;64(1):63–9. doi:10.3322/caac.21214.

    Article  PubMed  Google Scholar 

  9. Pelucchi C, Pira E, Piolatto G, Coggiola M, Carta P, La Vecchia C. Occupational silica exposure and lung cancer risk: a review of epidemiological studies 1996–2005. Ann Oncol. 2006;17(7):1039–50.

    Article  CAS  PubMed  Google Scholar 

  10. Finkelstein MM. Silica, silicosis, and lung cancer: a risk assessment. Am J Ind Med. 2000;38(1):8–18.

    Article  CAS  PubMed  Google Scholar 

  11. Uber CL, McReynolds RA. Immunotoxicology of silica. Crit Rev Toxicol. 1982;10(4):303–19.

    Article  CAS  PubMed  Google Scholar 

  12. Steenland K, Goldsmith DF. Silica exposure and autoimmune diseases. Am J Ind Med. 1995;28(5):603–8.

    Article  CAS  PubMed  Google Scholar 

  13. Mayes MD. Epidemiologic studies of environmental agents and systemic autoimmune diseases. Environ Health Perspect. 1999;107 Suppl 5:743–8.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Parks CG, Conrad K, Cooper GS. Occupational exposure to crystalline silica and autoimmune disease. Environ Health Perspect. 1999;107 Suppl 5:793–802.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Hess EV. Environmental chemicals and autoimmune disease: cause and effect. Toxicology. 2002;181–182:65–70.

    Article  PubMed  Google Scholar 

  16. Caplan A. Certain unusual radiological appearances in the chest of coal-miners suffering from rheumatoid arthritis. Thorax 8(1): 29–37. doi:10.1136/thx.8.1.29.

  17. Caplan A. Rheumatoid disease and pneumoconiosis (Caplan’s syndrome). Proc R Soc Med. 1959;52:1111–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Siltzbach LE. Diffuse pulmonary granulomatosis and fibroses. Mod Treat. 1964;15:290–306.

    Google Scholar 

  19. Rodnan GP, Benedek TG, Medsger Jr TA, Cammarata RJ. The association of progressive systemic sclerosis (scleroderma) with coal miners’ pneumoconiosis and other forms of silicosis. Ann Intern Med. 1967;66(2):323–34.

    Article  CAS  PubMed  Google Scholar 

  20. Haustein UF, Ziegler V, Herrmann K, Mehlhorn J, Schmidt C. Silica-induced scleroderma. J Am Acad Dermatol. 1990;22(3):444–8.

    Article  CAS  PubMed  Google Scholar 

  21. Haustein UF, Anderegg U. Silica induced scleroderma – clinical and experimental aspects. J Rheumatol. 1998;25(10):1917–26.

    CAS  PubMed  Google Scholar 

  22. Sanchez-Roman J, Wichmann I, Salaberri J, Varela JM, Nuñez-Roldan A. Multiple clinical and biological autoimmune manifestations in 50 workers after occupational exposure to silica. Ann Rheum Dis. 1993;52(7):534–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Koeger AC, Lang T, Alcaix D, Milleron B, Rozenberg S, Chaibi P, Arnaud J, Mayaud C, Camus JP, Bourgeois P. Silica-associated connective tissue disease. A study of 24 cases. Medicine (Baltimore). 1995;74(5):221–37.

    Article  CAS  Google Scholar 

  24. D’Cruz D. Autoimmune diseases associated with drugs, chemicals and environmental factors. Toxicol Lett. 2000;112–113:421–32.

    Article  PubMed  Google Scholar 

  25. Gregorini G, Tira P, Frizza J, D’Haese PC, Elseviers MM, Nuyts G, Maiorca R, De Broe ME. ANCA-associated diseases and silica exposure. Clin Rev Allergy Immunol. 1997;15(1):21–40.

    Article  CAS  PubMed  Google Scholar 

  26. Tervaert JW, Stegeman CA, Kallenberg CG. Silicon exposure and vasculitis. Curr Opin Rheumatol. 1998;10(1):12–7.

    Article  CAS  PubMed  Google Scholar 

  27. Mulloy KB. Silica exposure and systemic vasculitis. Environ Health Perspect. 2003;111(16):1933–8.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Bartůnková J, Pelclová D, Fenclová Z, Sedivá A, Lebedová J, Tesar V, Hladíková M, Klusácková P. Exposure to silica and risk of ANCA-associated vasculitis. Am J Ind Med. 2006;49(7):569–76.

    Article  PubMed  Google Scholar 

  29. Levine S, Sowinski R. Enhancement of allergic encephalomyelitis by particulate adjuvants inoculated long before antigen. Am J Pathol. 1980;99(2):291–304.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Stone OJ. Autoimmunity as a secondary phenomenon in scleroderma (and so-called human adjuvant disease). Med Hypotheses. 1991;34(2):127–30.

    Article  CAS  PubMed  Google Scholar 

  31. Rao TD, Frey AB. Administration of silica sensitizes lipopolysaccharide responsiveness of murine macrophages but inhibits T and B cell priming by inhibition of antigen presenting function. Immunol Investig. 1998;27(3):181–99.

    Article  CAS  Google Scholar 

  32. Wu P, Hyodoh F, Hatayama T, Sakaguchi H, Hatada S, Miura Y, Takata-Tomokuni A, Katsuyama H, Otsuki T. Induction of CD69 antigen expression in peripheral blood mononuclear cells on exposure to silica, but not by asbestos/chrysotile-A. Immunol Lett. 2005;98(1):145–52.

    Article  CAS  PubMed  Google Scholar 

  33. Hayashi H, Miura Y, Maeda M, Murakami S, Kumagai N, Nishimura Y, Kusaka M, Urakami K, Fujimoto W, Otsuki T. Reductive alteration of the regulatory function of the CD4(+)CD25(+) T cell fraction in silicosis patients. Int J Immunopathol Pharmacol. 2010;23(4):1099–109.

    CAS  PubMed  Google Scholar 

  34. Witkowska AM. On the role of sIL-2R measurements in rheumatoid arthritis and cancers. Mediat Inflamm. 2005;2005(3):121–30.

    Article  Google Scholar 

  35. Murakami S. Soluble interleukin-2 receptor in cancer. Front Biosci. 2004;9:3085–90.

    Article  CAS  PubMed  Google Scholar 

  36. Hayashi H, Maeda M, Murakami S, Kumagai N, Chen Y, Hatayama T, Katoh M, Miyahara N, Yamamoto S, Yoshida Y, Nishimura Y, Kusaka M, Fujimoto W, Otsuki T. Soluble interleukin-2 receptor as an indicator of immunological disturbance found in silicosis patients. Int J Immunopathol Pharmacol. 2009;22(1):53–62.

    CAS  PubMed  Google Scholar 

  37. Kabelitz D, Janssen O. Antigen-induced death of T-lymphocytes. Front Biosci. 1997;2:d61–77.

    Article  CAS  PubMed  Google Scholar 

  38. Maher S, Toomey D, Condron C, Bouchier-Hayes D. Activation-induced cell death: the controversial role of Fas and Fas ligand in immune privilege and tumour counterattack. Immunol Cell Biol. 2002;80(2):131–7.

    Article  CAS  PubMed  Google Scholar 

  39. Green DR, Droin N, Pinkoski M. Activation-induced cell death in T cells. Immunol Rev. 2003;193:70–81.

    Article  CAS  PubMed  Google Scholar 

  40. Cheng J, Zhou T, Liu C, Shapiro JP, Brauer MJ, Kiefer MC, Barr PJ, Mountz JD. Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science. 1994;263(5154):1759–62.

    Article  CAS  PubMed  Google Scholar 

  41. Tokano Y, Miyake S, Kayagaki N, Nozawa K, Morimoto S, Azuma M, Yagita H, Takasaki Y, Okumura K, Hashimoto H. Soluble Fas molecule in the serum of patients with systemic lupus erythematosus. J Clin Immunol. 1996;16(5):261–5.

    Article  CAS  PubMed  Google Scholar 

  42. Jodo S, Kobayashi S, Kayagaki N, Ogura N, Feng Y, Amasaki Y, Fujisaku A, Azuma M, Yagita H, Okumura K, Koike T. Serum levels of soluble Fas/APO-1 (CD95) and its molecular structure in patients with systemic lupus erythematosus (SLE) and other autoimmune diseases. Clin Exp Immunol. 1997;107(1):89–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Nozawa K, Kayagaki N, Tokano Y, Yagita H, Okumura K, Hasimoto H. Soluble Fas (APO-1, CD95) and soluble Fas ligand in rheumatic diseases. Arthritis Rheum. 1997;40(6):1126–9.

    Article  CAS  PubMed  Google Scholar 

  44. Tomokuni A, Aikoh T, Matsuki T, Isozaki Y, Otsuki T, Kita S, Ueki H, Kusaka M, Kishimoto T, Ueki A. Elevated soluble Fas/APO-1 (CD95) levels in silicosis patients without clinical symptoms of autoimmune diseases or malignant tumours. Clin Exp Immunol. 1997;110(2):303–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Otsuki T, Sakaguchi H, Tomokuni A, Aikoh T, Matsuki T, Kawakami Y, Kusaka M, Ueki H, Kita S, Ueki A. Soluble Fas mRNA is dominantly expressed in cases with silicosis. Immunology. 1998;94(2):258–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Otsuki T, Sakaguchi H, Tomokuni A, Aikoh T, Matsuki T, Isozaki Y, Hyodoh F, Kawakami Y, Kusaka M, Kita S, Ueki A. Detection of alternatively spliced variant messages of Fas gene and mutational screening of Fas and Fas ligand coding regions in peripheral blood mononuclear cells derived from silicosis patients. Immunol Lett. 2000;72(2):137–43.

    Article  CAS  PubMed  Google Scholar 

  47. Yu KY, Kwon B, Ni J, Zhai Y, Ebner R, Kwon BS. A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis. J Biol Chem. 1999;274(20):13733–6.

    Article  CAS  PubMed  Google Scholar 

  48. Lin WW, Hsieh SL. Decoy receptor 3: a pleiotropic immunomodulator and biomarker for inflammatory diseases, autoimmune diseases and cancer. Biochem Pharmacol. 2011;81(7):838–47. doi:10.1016/j.bcp.2011.01.011.

    Article  CAS  PubMed  Google Scholar 

  49. Siakavellas SI, Sfikakis PP, Bamias G. The TL1A/DR3/DcR3 pathway in autoimmune rheumatic diseases. Semin Arthritis Rheum. 2015;45(1):1–8. doi:10.1016/j.semarthrit.2015.02.007.

    Article  CAS  PubMed  Google Scholar 

  50. Pitti RM, Marsters SA, Lawrence DA, Roy M, Kischkel FC, Dowd P, Huang A, Donahue CJ, Sherwood SW, Baldwin DT, Godowski PJ, Wood WI, Gurney AL, Hillan KJ, Cohen RL, Goddard AD, Botstein D, Ashkenazi A. Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature. 1998;396(6712):699–703.

    Article  CAS  PubMed  Google Scholar 

  51. Otsuki T, Tomokuni A, Sakaguchi H, Aikoh T, Matsuki T, Isozaki Y, Hyodoh F, Ueki H, Kusaka M, Kita S, Ueki A. Over-expression of the decoy receptor 3 (DcR3) gene in peripheral blood mononuclear cells (PBMC) derived from silicosis patients. Clin Exp Immunol. 2000;119(2):323–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Sakaguchi S, Sakaguchi N, Shimizu J, Yamazaki S, Sakihama T, Itoh M, Kuniyasu Y, Nomura T, Toda M, Takahashi T. Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev. 2001;182:18–32.

    Article  CAS  PubMed  Google Scholar 

  53. Takahashi T, Sakaguchi S. Naturally arising CD25+CD4+ regulatory T cells in maintaining immunologic self-tolerance and preventing autoimmune disease. Curr Mol Med. 2003;3(8):693–706.

    Article  CAS  PubMed  Google Scholar 

  54. Afzali B, Lombardi G, Lechler RI, Lord GM. The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease. Clin Exp Immunol. 2007;148(1):32–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Chen Z, O’Shea JJ. Th17 cells: a new fate for differentiating helper T cells. Immunol Res. 2008;41(2):87–102. doi:10.1007/s12026-007-8014-9.

    Article  CAS  PubMed  Google Scholar 

  56. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Annu Rev Immunol. 2009;27:485–517. doi:10.1146/annurev.immunol.021908.132710.

    Article  CAS  PubMed  Google Scholar 

  57. O’Connor RA, Taams LS, Anderton SM. Translational mini-review series on Th17 cells: CD4 T helper cells: functional plasticity and differential sensitivity to regulatory T cell-mediated regulation. Clin Exp Immunol. 2010;159(2):137–47. doi:10.1111/j.1365-2249.2009.04040.x.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Girtsman T, Jaffar Z, Ferrini M, Shaw P, Roberts K. Natural Foxp3(+) regulatory T cells inhibit Th2 polarization but are biased toward suppression of Th17-driven lung inflammation. J Leukoc Biol. 2010;88(3):537–46. doi:10.1189/jlb.0110044.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Muranski P, Restifo NP. Essentials of Th17 cell commitment and plasticity. Blood. 2013;121(13):2402–14. doi:10.1182/blood-2012-09-378653.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Wu P, Miura Y, Hyodoh F, Nishimura Y, Hatayama T, Hatada S, Sakaguchi H, Kusaka M, Katsuyama H, Tomita M, Otsuki T. Reduced function of CD4+25+ regulatory T cell fraction in silicosis patients. Int J Immunopathol Pharmacol. 2006;19(2):357–68.

    CAS  PubMed  Google Scholar 

  61. Takata-Tomokuni A, Ueki A, Shiwa M, Isozaki Y, Hatayama T, Katsuyama H, Hyodoh F, Fujimoto W, Ueki H, Kusaka M, Arikuni H, Otsuki T. Detection, epitope-mapping and function of anti-Fas autoantibody in patients with silicosis. Immunology. 2005;116(1):21–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Ohtsuki T, Yawata Y, Wada H, Sugihara T, Mori M, Namba M. Two human myeloma cell lines, amylase-producing KMS-12-PE and amylase-non-producing KMS-12-BM, were established from a patient, having the same chromosome marker, t(11;14)(q13;q32). Br J Haematol. 1989;73(2):199–204.

    Article  CAS  PubMed  Google Scholar 

  63. Ueki A, Isozaki Y, Tomokuni A, Hatayama T, Ueki H, Kusaka M, Shiwa M, Arikuni H, Takeshita T, Morimoto K. Intramolecular epitope spreading among anti-caspase-8 autoantibodies in patients with silicosis, systemic sclerosis and systemic lupus erythematosus, as well as in healthy individuals. Clin Exp Immunol. 2002;129(3):556–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Ueki A, Isozaki Y, Kusaka M. Anti-caspase-8 autoantibody response in silicosis patients is associated with HLA-DRB1, DQB1 and DPB1 alleles. J Occup Health. 2005;47(1):61–7.

    Article  CAS  PubMed  Google Scholar 

  65. Ueki H, Kohda M, Nobutoh T, Yamaguchi M, Omori K, Miyashita Y, Hashimoto T, Komai A, Tomokuni A, Ueki A. Antidesmoglein autoantibodies in silicosis patients with no bullous diseases. Dermatology. 2001;202(1):16–21.

    Article  CAS  PubMed  Google Scholar 

  66. Ueki A, Isozaki Y, Tomokuni A, Tanaka S, Otsuki T, Kishimoto T, Kusaka M, Aikoh T, Sakaguchi H, Hydoh F. Autoantibodies detectable in the sera of silicosis patients. The relationship between the anti-topoisomerase I antibody response and HLA-DQB1*0402 allele in Japanese silicosis patients. Sci Total Environ. 2001;270(1–3):141–8.

    Article  CAS  PubMed  Google Scholar 

  67. Tomokuni A, Otsuki T, Sakaguchi H, Isozaki Y, Hyodoh F, Kusaka M, Ueki A. Detection of anti-topoisomerase I autoantibody in patients with silicosis. Environ Health Prev Med. 2002;7(1):7–10. doi:10.1007/BF02898059.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Maeda M, Nishimura Y, Kumagai N, Hayashi H, Hatayama T, Katoh M, Miyahara N, Yamamoto S, Hirastuka J, Otsuki T. Dysregulation of the immune system caused by silica and asbestos. J Immunotoxicol. 2010;7(4):268–78. doi:10.3109/1547691X.2010.512579.

    Article  CAS  PubMed  Google Scholar 

  69. Lee S, Hayashi H, Maeda M, Chen Y, Matsuzaki H, Takei-Kumagai N, Nishimura Y, Fujimoto W, Otsuki T. Environmental factors producing autoimmune dysregulation – chronic activation of T cells caused by silica exposure. Immunobiology. 2012;217(7):743–8. doi:10.1016/j.imbio.2011.12.009.

    Article  CAS  PubMed  Google Scholar 

  70. Lee S, Matsuzaki H, Kumagai-Takei N, Yoshitome K, Maeda M, Chen Y, Kusaka M, Urakami K, Hayashi H, Fujimoto W, Nishimura Y, Otsuki T. Silica exposure and altered regulation of autoimmunity. Environ Health Prev Med. 2014;19(5):322–9. doi:10.1007/s12199-014-0403-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Kumagai N, Hayashi H, Maeda M, Miura Y, Nishimura Y, Matsuzaki H, Lee S, Fujimoto W, Otsuki T. Immunological effects of silica and related dysregulation of autoimmunity. In: Mavragani CP, editor. Autoimmune disorders – pathogenetic aspects. Rijeka: InTech Open Access Publisher; 2011. p. 157–74.

    Google Scholar 

  72. Hayashi H, Nishimura Y, Hyodo F, Maeda M, Kumagai N, Miura Y, Kusaka M, Uragami K, Otsuki T. Dysregulation of autoimmunity caused by silica exposure: fas-mediated apoptosis in T lymphocytes derived from silicosis patients. In: Petri M, editor. Autoimmune disorders: symptoms, diagnosis and treatment. Hauppauge: Nova Science Publishers; 2011. p. 293–301.

    Google Scholar 

  73. Takei-Kumagai N, Lee S, Matsuzaki H, Hayashi H, Maeda M, Nishimura Y, Otsuki T. Silica, immunological effects. In: Uversky VN, Kretsinger RH, Permyakov EA, editors. Encyclopedia of metalloproteins. New York: Springer Science+Business Media; 2013. p. 1956–71.

    Google Scholar 

  74. Lee S, Maeda M, Hayashi H, Matsuzaki H, Kumagai-Takei N, Nishimura Y. Otsuki Immunostimulation by silica particles and the development of autoimmune dysregulation. In: Guy Huynh Thien D, editor. Immune response activation. Rijeka: InTech publisher; 2014. p. 249–65.

    Google Scholar 

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Acknowledgments

The authors thank former colleagues in the Department of Hygiene, Kawasaki Medical School, namely, Prof. Ayako Ueki, Drs. Fuminori Hyodoh, Akiko Takata-Tomokuni, Yasuhiko Kawakami, Takaaki Aikoh, Shuko Murakami, and Yoshie Miura. We also appreciate the technical assistance of Ms. Haruko Sakaguchi, Naomi Miyahara, Minako Katoh, and Yumika Isozaki. We express special thanks to Drs. Masayasu Kusaka and Kozo Urakami for coordinating the collection of clinical samples. Part of the experimental results in this article was supported by the Special Coordination Fund for Promoting Science and Technology (H18-1-3-3-1, “Comprehensive approach on asbestos-related diseases”), KAKENHI grants (18390186, 19659153, 20390178, and 25460825), Kawasaki Medical School Project grants (20-410I, 23S5, 24S6, 25B65, and 27B06), the Sumitomo Foundation Grant (053027), the Yasuda Memorial Foundation Grant (H18), funding from the Takeda Science Foundation (I-2008) and Young Investigator Activating Grant from the Japanese Society of Hygiene (H18), the Ryobi Teien Memorial Foundation (H24), and the Kawasaki Foundation for Medical Science and Medical Welfare (H24).

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Authors and Affiliations

  1. Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan

    Suni Lee, Hidenori Matsuzaki, Naoko Kumagai-Takei, Kei Yoshitome, Shoko Yamamoto, Tamayo Hatayama, Yasumitsu Nishimura & Takemi Otsuki

  2. Department of Dermatology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan

    Hiroaki Hayashi

  3. Department of Biofunctional Chemistry, Division of Bioscience, Okayama University Graduate School of Natural Science and Technology, 1-1-1 Tsushima-Naka, Kita-Ku, Okayama, 7008530, Japan

    Megumi Maeda

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  1. Suni Lee
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Correspondence to Takemi Otsuki .

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Editors and Affiliations

  1. Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan

    Takemi Otsuki

  2. Immuntotoxicology and Allergy Unit & Occupational Biorepository, Center of Excellence on Aging and Translational Medicine (CeSI-MeT), “G. D’Annunzio” University Foundation, Chieti, Italy

    Claudia Petrarca

  3. Immuntotoxicology and Allergy Unit & Occupational Biorepository, Center of Excellence on Aging and Translational Medicine (CeSI-MeT), “G. D’Annunzio” University Foundation, Chieti, Italy

    Mario Di Gioacchino

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Lee, S. et al. (2017). Silica-Induced Immunotoxicity: Chronic and Aberrant Activation of Immune Cells. In: Otsuki, T., Petrarca, C., Di Gioacchino, M. (eds) Allergy and Immunotoxicology in Occupational Health. Current Topics in Environmental Health and Preventive Medicine. Springer, Singapore. https://doi.org/10.1007/978-981-10-0351-6_2

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