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Cheryl E Rockwell, Mingcai Zhang, Patrick E Fields, Curtis D Klaassen, Th2 Skewing by Activation of Nrf2 in CD4+ T Cells, The Journal of Immunology, Volume 188, Issue 4, February 2012, Pages 1630–1637, https://doi.org/10.4049/jimmunol.1101712
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Abstract
NF erythroid 2-related factor 2 (Nrf2) is a transcription factor that mediates the upregulation of a battery of cytoprotective genes in response to cell stress. Recent studies showed that Nrf2 also modulates immune responses and exhibits anti-inflammatory activity. In this article, we demonstrate that a common food preservative, tert-butylhydroquinone, can activate Nrf2 in T cells, as evidenced by Nrf2 binding to the antioxidant response element and the subsequent upregulation of Nrf2 target genes. The activation of Nrf2 suppresses IFN-γ production, while inducing the production of the Th2 cytokines IL-4, IL-5, and IL-13. Nrf2 activation also suppresses T-bet DNA binding and promotes GATA-binding protein 3 DNA binding. Collectively, the present studies suggested that Nrf2 activation skews CD4+ T cells toward Th2 differentiation and, thus, represents a novel regulatory mechanism in CD4+ T cells. Further studies are needed to determine whether the commercial use of Nrf2 activators as food preservatives promotes food allergies in humans.
