American Association of Immunologists, The Journal of Immunology, 1_Supplement(196), p. 73.1-73.1, 2016
DOI: 10.4049/jimmunol.196.supp.73.1
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Abstract Cells undergoing xenobiotic or oxidative stress activate the transcription factor Nrf2, which initiates an intrinsic “stress surveillance” pathway involving detoxifying enzymes. We recently found that the cytokine IL-17D effects a form of extrinsic stress surveillance by inducing antitumor immunity, but how IL-17D is regulated remains unknown. Here, we show that Nrf2 induced IL-17D directly in primary tumors as well as during viral infection in vivo. Expression of IL-17D in tumors and virally infected cells is essential for optimal protection of the host as il17d−/− mice experienced a higher incidence of tumors and exacerbated viral infections compared to WT animals. Moreover, activating Nrf2 to induce IL-17D in established tumors led to NK cell-dependent tumor regression. These data demonstrate that Nrf2 can initiate both intrinsic and extrinsic stress surveillance pathways and highlight the use of Nrf2 agonists as immune therapies for cancer and infection.