Silica exposure and altered regulation of autoimmunity

Our plain-English summary of Silica exposure and altered regulation of autoimmunity, by S. Lee, H. Matsuzaki, N. Kumagai-Takei, et al (Environmental Health and Preventive Medicine, 2014).

The study

• Authors: S. Lee, H. Matsuzaki, N. Kumagai-Takei, K. Yoshitome, M. Maeda, Y. Chen, M. Kusaka, K. Urakami, H. Hayashi, W. Fujimoto, Y. Nishimura, T. Otsuki
• Journal: Environmental Health and Preventive Medicine
• Published: 2014;19(5):322-9
• Type of article: Review
• Cited by: 32 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Silica particles and asbestos fibers, which are known as typical causatives of pneumoconiosis, induce lung fibrosis. Moreover, silicosis patients often complicate with autoimmune diseases, and asbestos-exposed patients suffer from malignant diseases such as pleural mesothelioma and lung cancer. We have been conducting experimental studies to investigate altered regulation of self-tolerance caused by silica exposure, including analyses using specimens such as plasma and immunocompetent cells obtained from silicosis patients, as a means of examining the supposition that silica exposure induces molecular and cellular biological alterations of immune cells. These approaches have resulted in the detection of several specific autoantibodies, alterations of CD95/Fas and its related molecules, and evidence of chronic activation of responder T cells and regulatory T cells following silica exposure. In this review, we present details of our investigations as an introduction to scientific approaches examining the immunological effects of environmental and occupational substances.

In plain English

This was a review of the authors' own earlier studies of how silica exposure may disturb immune control of autoimmunity. It was about silica; asbestos was mentioned as background and in one laboratory comparison. The silicosis patients were brickyard workers in Bizen City, Japan, without clinical symptoms of autoimmune disease or malignant tumors. The review did not give their number. Compared with healthy donors, patients had higher anti-nuclear antibody titers and significantly higher serum soluble Fas, which can block a cell-death pathway. Anti-Fas autoantibody was found in one quarter of patients. Soluble IL-2 receptor levels tended to fall between those of healthy donors and systemic sclerosis patients, but differences were not significant. Regulatory T cells from patients showed significantly higher Fas expression and more cell death when exposed to an anti-Fas antibody. When healthy donors' blood cells were cultured with silica particles, T cells became activated, but not if monocytes were removed; chrysotile asbestos did not induce the activation marker CD69. The authors concluded that chronic silica exposure unbalanced regulatory and responder T cells, which may lead to autoimmune disease.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of the authors' own research group's earlier experimental and clinical-specimen studies
• Who was studied: Silicosis patients who were brickyard workers in Bizen City, Okayama Prefecture, Japan, diagnosed by the ILO 2000 guideline, without clinical symptoms of autoimmune disease or malignant tumors, compared with healthy donors (and in some analyses systemic sclerosis patients). Numbers of patients and study dates are not given in the review.
• Exposure: Occupational silica exposure (silicosis). In laboratory experiments, blood cells from healthy donors were cultured with silica particles. One experiment also used chrysotile asbestos.
• Main results:
  • Silicosis patients showed higher titers of anti-nuclear antibodies than healthy donors.
  • Anti-CD95/Fas autoantibody was detected in one quarter of silicosis patients.
  • Serum soluble Fas levels were significantly higher in silicosis patients than in healthy donors.
  • Serum soluble IL-2 receptor levels in silicosis patients tended to be higher than in healthy donors and lower than in systemic sclerosis patients, but the differences between groups were not significant.
  • Factor analysis suggested a subgroup of silicosis patients who worsened immunologically rather than in respiratory terms.
  • Regulatory T cells from silicosis patients showed significantly higher Fas expression than those of healthy donors. Their apoptosis with agonistic anti-Fas antibody was also significantly more frequent and greater.
  • When peripheral blood mononuclear cells from healthy donors were cultured with silica particles, T cells expressed the activation marker CD69. Activation did not occur when monocytes were removed. Chrysotile did not induce CD69.
  • Culturing healthy donors' blood cells with silica reduced the percentage of FoxP3 positive cells among CD25 positive cells over 4 days.
• The authors' conclusion: The authors concluded that chronic silica exposure produced an imbalance between regulatory T cells and responder T cells in silicosis patients. They said this may lead to altered regulation of autoimmunity and autoimmune diseases.
• Limitations the authors state:
  • The authors had not yet investigated the effects of silica on Th17 cells or dendritic cells.
  • In the regulatory T cell function assay, cells were not sorted by FoxP3. The authors noted the CD4 and CD25 positive fraction from silicosis patients may have been contaminated by activated responder T cells.
  • The authors stated it was not fully understood why lung function (FEV1.0) grouped with some immunological factors, and that further study is needed.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Construction.

Medical terms in this study, explained in our Lexicon: Pneumoconiosis, Fibrosis, Silicosis, Pleural Mesothelioma, Lung Cancer.

Related studies

• Silicosis and autoimmunity — S. Lee, H. Hayashi, et al. (2017)
• Expression of the T cell receptor Vbeta repertoire in a human T cell resistant to asbestos-induced apoptosis and peripheral blood T cells from patients with silica and asbestos-related diseases — Y. Nishimura, Y. Miura, et al. (2006)
• Environmental factors and human health: fibrous and particulate substance-induced immunological disorders and construction of a health-promoting living environment — T. Otsuki, H. Matsuzaki, et al. (2016)
• Silicosis and smoking strongly increase lung cancer risk in silica-exposed workers — N. Kurihara, O. Wada (2004)
• Dysregulation of the immune system caused by silica and asbestos — M. Maeda, Y. Nishimura, et al. (2010)
• One agent, many diseases: exposure-response data and comparative risks of different outcomes following silica exposure — K. Steenland (2005)

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