Environmental pollutants and the immune response

Abstract

Environmental pollution is one of the most serious challenges to health in the modern world. Pollutants alter immune responses and can provoke immunotoxicity. In this Review, we summarize the major environmental pollutants that are attracting wide-ranging concern and the molecular basis underlying their effects on the immune system. Xenobiotic receptors, including the aryl hydrocarbon receptor (AHR), sense and respond to a subset of environmental pollutants by activating the expression of detoxification enzymes to protect the body. However, chronic activation of the AHR leads to immunotoxicity. KEAP1–NRF2 is another important system that protects the body against environmental pollutants. KEAP1 is a sensor protein that detects environmental pollutants, leading to activation of the transcription factor NRF2. NRF2 protects the body from immunotoxicity by inducing the expression of genes involved in detoxification, antioxidant and anti-inflammatory activities. Intervening in these sensor–response systems could protect the body from the devastating immunotoxicity that can be induced by environmental pollutants.

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Fig. 1: Differential responses of the body to low-dose and high-dose environmental electrophiles.
Fig. 2: The AHR and KEAP1–NRF2 system sense environmental chemicals and regulate the expression of detoxifying genes.
Fig. 3: The AHR and KEAP1–NRF2 system.

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Acknowledgements

We thank T. O’Connor at Trinity College Dublin for critical reading and professional editing of the manuscript. This work was supported in part by MEXT/JSPS KAKENHI (19H05649 to M. Y. and 17KK0183 and 19K07340 to T. S.), the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED under grant no. JP20am0101095, the Project for Development of Innovative Research on Cancer Therapeutics (P-DIRECT) from AMED under grant no. JP20cm0106101, the Core Research for Evolutional Science and Technology (CREST) (chronic inflammation) from AMED, and the Takeda Science Foundation (T.S.).

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Suzuki, T., Hidaka, T., Kumagai, Y. et al. Environmental pollutants and the immune response. Nat Immunol (2020). https://doi.org/10.1038/s41590-020-0802-6

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