Accelerated cell cycle progression of human regulatory T cell-like cell line caused by continuous exposure to asbestos fibers

Our plain-English summary of Accelerated cell cycle progression of human regulatory T cell-like cell line caused by continuous exposure to asbestos fibers, by S. Lee, H. Matsuzaki, M. Maeda, et al (International Journal of Oncology, 2017).

The study

• Authors: S. Lee, H. Matsuzaki, M. Maeda, S. Yamamoto, N. Kumagai-Takei, T. Hatayama, M. Ikeda, K. Yoshitome, Y. Nishimura, T. Otsuki
• Journal: International Journal of Oncology
• Published: 2017;50(1):66-74
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos exposure causes malignant tumors such as lung cancer and malignant mesothelioma. Based on our hypothesis in which continuous exposure to asbestos of immune cells cause reduction of antitumor immunity, the decrease of natural killer cell killing activity with reduction of NKp46 activating receptor expression, inhibition of cytotoxic T cell clonal expansion, reduced CXCR3 chemokine receptor expression and production of interferon-γ production in CD4+ T cells were reported using cell line models, freshly isolated peripheral blood immune cells from health donors as well as asbestos exposed patients such as pleural plaque and mesothelioma. In addition to these findings, regulatory T cells (Treg) showed enhanced function through cell-cell contact and increased secretion of typical soluble factors, interleukin (IL)-10 and transforming growth factor (TGF)-β, in a cell line model using the MT-2 human polyclonal T cells and its sublines exposed continuously to asbestos fibers. Since these sublines showed a remarkable reduction of FoxO1 transcription factor, which regulates various cell cycle regulators in asbestos-exposed sublines, the cell cycle progression in these sublines was examined and compared with that of the original MT-2 cells. Results showed that cyclin D1 expression was markedly enhanced, and various cyclin-dependent kinase-inhibitors were reduced with increased S phases in the sublines. Furthermore, the increase of cyclin D1 expression was regulated by FoxO1. The overall findings indicate that antitumor immunity in asbestos-exposed individuals may be reduced in Treg through changes in the function and volume of Treg.

In plain English

This was a laboratory study of cells, not of people. The authors used MT-2, a human T cell line reported to act like regulatory T cells, which are immune cells that hold back other immune responses. They compared the original cells with seven sublines kept in contact with chrysotile A, chrysotile B or crocidolite asbestos for more than one year. In all sublines, mRNA for cyclin D1, a protein that drives cell division, was about 20-60-fold higher than in the original cells. Several cell cycle inhibitors were lower. The ratio of cells in the DNA-copying S phase to cells in G1 phase was 2.6 to 4.3 times that of the original cells. Artificially lowering FoxO1 in the original cells significantly raised cyclin D1, though less than in the sublines. FoxO1 is a gene already found to be low in the sublines. The authors concluded that antitumor immunity in asbestos-exposed people may be reduced through changes in regulatory T cell function and numbers. They noted this is hard to test in patients, because these cells would need to be studied around tumors, not in blood.

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: Laboratory (in vitro) study of a human T cell line and sublines grown with asbestos over long periods. Measured were cell cycle regulator expression, cell cycle phases, and the effect of artificially silencing FoxO1.
• Who was studied: The original MT-2 cell line (an HTLV-1 immortalized human polyclonal T cell line reported to have regulatory T cell function) and seven sublines derived from it: CA1-3, CB1-3 and CR1. Work was done at Kawasaki Medical School and Okayama University, Japan. No study dates are given.
• Exposure: Continuous exposure for more than one year to chrysotile A (sublines CA1-3), chrysotile B (CB1-3) or crocidolite (CR1) at 5-10 µg/ml. When given briefly, these doses caused less than half of the cells to undergo apoptosis (programmed cell death).
• Main results:
  • In all asbestos-exposed sublines, cyclin D1 mRNA was increased about 20-60-fold compared with the original MT-2 cells.
  • Cyclins D2 and E showed no differences between the original cells and the sublines. Cyclins A and B were lower in the sublines, at 0.2-0.5-fold.
  • The cyclin-dependent kinase inhibitors p21Cip1, p57Kip2, p18ink4c and p19ink4d showed significantly reduced mRNA expression in the sublines.
  • At the protein level, cyclin D1 was higher in the sublines than in the original cells, and p21Cip1 and p16ink4a were reduced.
  • The ratio of S phase to G1 phase cells, set at 1.0 for the original MT-2 cells, ranged from 2.6 to 4.3 in all sublines.
  • Artificially knocking down FoxO1 in the original MT-2 cells (clone KD#1) significantly increased cyclin D1 mRNA compared with control cells. The increase was not as large as in the sublines exposed to asbestos for more than one year.
• The authors' conclusion: The authors concluded that antitumor immunity in asbestos-exposed individuals may be reduced through changes in the function and volume (numbers) of regulatory T cells. In the discussion they state that their cell line model showed asbestos causes a reduction of antitumor immunity in asbestos-exposed individuals.
• Limitations the authors state:
  • The authors state that these effects are difficult to examine in asbestos-exposed patients, because regulatory T cells would need to be analyzed in the area surrounding tumors rather than in peripheral blood.
  • The authors state that p16ink4a mRNA results were not representative because of the lower quality of the real-time RT-PCR, so protein results were relied on for p16ink4a.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Asbestos Exposure, Lung Cancer, Malignant Mesothelioma, Pleural Plaques, Mesothelioma.

Related studies

• Aberrant expression of FoxP3 in a human T cell line possessing regulatory T cell‑like function and exposed continuously to asbestos fibers — M. Maeda, H. Matsuzaki, et al. (2018)
• Enhancement of regulatory T cell-like suppressive function in MT-2 by long-term and low-dose exposure to asbestos — C. Ying, M. Maeda, et al. (2015)
• Alteration of cytoskeletal molecules in a human T cell line caused by continuous exposure to chrysotile asbestos — M. Maeda, Y. Chen, et al. (2013)
• FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line — H. Matsuzaki, S. Lee, et al. (2016)
• Increased production of matrix metalloproteinase-7 (MMP-7) by asbestos exposure enhances tissue migration of human regulatory T-like cells — S. Lee, S. Yamamoto, et al. (2021)
• Reduction of CXC chemokine receptor 3 in an in vitro model of continuous exposure to asbestos in a human T-cell line, MT-2 — M. Maeda, Y. Nishimura, et al. (2011)

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