Nrf2 Induces IL-17D to Mediate Tumor and Virus Surveillance
Cells undergoing xenobiotic or oxidative stress activate the transcription factor nuclear factor erythroid-derived 2-like 2 (Nrf2), which initiates an intrinsic “stress surveillance” pathway. We recently found that the cytokine IL-17D effects a form of extrinsic stress surveillance by inducing antit...
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doaj-ac468b8017164efb8c90cff21f7339e82020-11-24T21:55:28ZengElsevierCell Reports2211-12472016-08-011692348235810.1016/j.celrep.2016.07.075Nrf2 Induces IL-17D to Mediate Tumor and Virus SurveillanceRobert Saddawi-Konefka0Ruth Seelige1Emilie T.E. Gross2Eric Levy3Stephen C. Searles4Allen Washington Jr.5Endi K. Santosa6Beichen Liu7Timothy E. O’Sullivan8Olivier Harismendy9Jack D. Bui10Department of Pathology, University of California, San Diego, San Diego, CA 92093, USADepartment of Pathology, University of California, San Diego, San Diego, CA 92093, USADepartment of Pathology, University of California, San Diego, San Diego, CA 92093, USAMoores Cancer Center Oncogenomics Laboratory, University of California, San Diego, San Diego, CA 92093, USADepartment of Pathology, University of California, San Diego, San Diego, CA 92093, USADepartment of Pathology, University of California, San Diego, San Diego, CA 92093, USADepartment of Pathology, University of California, San Diego, San Diego, CA 92093, USADepartment of Pathology, University of California, San Diego, San Diego, CA 92093, USAImmunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USAMoores Cancer Center Oncogenomics Laboratory, University of California, San Diego, San Diego, CA 92093, USADepartment of Pathology, University of California, San Diego, San Diego, CA 92093, USACells undergoing xenobiotic or oxidative stress activate the transcription factor nuclear factor erythroid-derived 2-like 2 (Nrf2), which initiates an intrinsic “stress surveillance” pathway. 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 in cancer cell lines. Moreover, both Nrf2 and IL-17D were induced 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 wild-type (WT) animals. Moreover, activating Nrf2 to induce IL-17D in established tumors led to natural killer 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.http://www.sciencedirect.com/science/article/pii/S221112471631021Ximmunosurveillanceinnate immunityinterleukin-17DNK cellsNrf2tumor rejection |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Robert Saddawi-Konefka Ruth Seelige Emilie T.E. Gross Eric Levy Stephen C. Searles Allen Washington Jr. Endi K. Santosa Beichen Liu Timothy E. O’Sullivan Olivier Harismendy Jack D. Bui |
spellingShingle |
Robert Saddawi-Konefka Ruth Seelige Emilie T.E. Gross Eric Levy Stephen C. Searles Allen Washington Jr. Endi K. Santosa Beichen Liu Timothy E. O’Sullivan Olivier Harismendy Jack D. Bui Nrf2 Induces IL-17D to Mediate Tumor and Virus Surveillance Cell Reports immunosurveillance innate immunity interleukin-17D NK cells Nrf2 tumor rejection |
author_facet |
Robert Saddawi-Konefka Ruth Seelige Emilie T.E. Gross Eric Levy Stephen C. Searles Allen Washington Jr. Endi K. Santosa Beichen Liu Timothy E. O’Sullivan Olivier Harismendy Jack D. Bui |
author_sort |
Robert Saddawi-Konefka |
title |
Nrf2 Induces IL-17D to Mediate Tumor and Virus Surveillance |
title_short |
Nrf2 Induces IL-17D to Mediate Tumor and Virus Surveillance |
title_full |
Nrf2 Induces IL-17D to Mediate Tumor and Virus Surveillance |
title_fullStr |
Nrf2 Induces IL-17D to Mediate Tumor and Virus Surveillance |
title_full_unstemmed |
Nrf2 Induces IL-17D to Mediate Tumor and Virus Surveillance |
title_sort |
nrf2 induces il-17d to mediate tumor and virus surveillance |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2016-08-01 |
description |
Cells undergoing xenobiotic or oxidative stress activate the transcription factor nuclear factor erythroid-derived 2-like 2 (Nrf2), which initiates an intrinsic “stress surveillance” pathway. 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 in cancer cell lines. Moreover, both Nrf2 and IL-17D were induced 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 wild-type (WT) animals. Moreover, activating Nrf2 to induce IL-17D in established tumors led to natural killer 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. |
topic |
immunosurveillance innate immunity interleukin-17D NK cells Nrf2 tumor rejection |
url |
http://www.sciencedirect.com/science/article/pii/S221112471631021X |
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