Th2 skewing by activation of Nrf2 in CD4+ T cells1

نویسندگان

  • Cheryl E. Rockwell
  • Mingcai Zhang
  • Patrick E. Fields
  • Curtis D. Klaassen
چکیده

Nuclear factor 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 have shown that Nrf2 also modulates immune responses and exhibits anti-inflammatory activity. In this report, we demonstrate that a common food preservative, tBHQ, can activate Nrf2 in T cells, as evidenced by Nrf2 binding to the antioxidant response element (ARE) and the subsequent upregulation of Nrf2 target genes. The activation of Nrf2 suppresses IFNγ 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-3 DNA binding. Collectively, the present studies suggest that Nrf2 activation skews CD4+ T cells toward Th2 differentiation and thus represents a novel regulatory mechanism in CD4+ T cells. Further studies will be needed to determine whether the commercial use of Nrf2 activators as food preservatives promotes food allergies in humans.

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Th2 skewing by activation of Nrf2 in CD4(+) T cells.

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تاریخ انتشار 2012