The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
STING-Mediated DNA Sensing Promotes Antitumor and Autoimmune Responses to Dying Cells
Open accessAbstract
Adaptive immune responses to Ags released by dying cells play a critical role in the development of autoimmunity, allograft rejection, and spontaneous as well as therapy-induced tumor rejection. Although cell death in these situations is considered sterile, various reports have implicated type I IFNs as drivers of the ensuing adaptive immune response to cell-associated Ags. However, the mechanisms that underpin this type I IFN production are poorly defined. In this article, we show that dendritic cells (DCs) can uptake and sense nuclear DNA-associated entities released by dying cells to induce type I IFN. Remarkably, this molecular pathway requires STING, but not TLR or NLR function, and results in the activation of IRF3 in a TBK1-dependent manner. DCs are shown to depend on STING function in vivo to efficiently prime IFN-dependent CD8+ T cell responses to tumor Ags. Furthermore, loss of STING activity in DCs impairs the generation of follicular Th cells and plasma cells, as well as anti-nuclear Abs, in an inducible model of systemic lupus erythematosus. These findings suggest that the STING pathway could be manipulated to enable the rational design of immunotherapies that enhance or diminish antitumor and autoimmune responses, respectively.
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Citations
Cites
STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
Ishikawa, H., Ma, Z., & Barber, G. N. (2009) · Nature · doi:10.1038/nature08476 · Cited by 2,759
CGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING.
Ablasser, A., Goldeck, M., Cavlar, T., Deimling, T., Witte, G., Röhl, I., Hopfner, K.-P., Ludwig, J., & Hornung, V. (2013) · Nature · doi:10.1038/nature12306 · Cited by 1,695
CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes
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Self-citationSTING is a direct innate immune sensor of cyclic di-GMP
Burdette, D. L., Monroe, K. M., Sotelo-Troha, K., Iwig, J. S., Eckert, B., Hyodo, M., Hayakawa, Y., & Vance, R. E. (2011) · Nature · doi:10.1038/nature10429 · Cited by 1,570
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Immunogenic and tolerogenic cell death
Green, D. R., Ferguson, T., Zitvogel, L., & Kroemer, G. (2009) · Nature Reviews Immunology · doi:10.1038/nri2545 · Cited by 1,176
Type I interferon is selectively required by dendritic cells for immune rejection of tumors
Diamond, M. S., Kinder, M., Matsushita, H., Mashayekhi, M., Dunn, G. P., Archambault, J. M., Lee, H., Arthur, C. D., White, J. M., Kalinke, U., et al. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20101158 · Cited by 1,081
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CD4+ T-cell help controls CD8+ T-cell memory via TRAIL-mediated activation-induced cell death
Janssen, E. M., Droin, N. M., Lemmens, E. E., Pinkoski, M. J., Bensinger, S. J., Ehst, B. D., Griffith, T. S., Green, D. R., & Schoenberger, S. P. (2005) · Nature · doi:10.1038/nature03337 · Cited by 619
Self-citationSTING and the innate immune response to nucleic acids in the cytosol
Burdette, D. L., & Vance, R. E. (2013) · Nature Immunology · doi:10.1038/ni.2491 · Cited by 501
Cited by
STING: infection, inflammation and cancer.
Barber, G. N. (2015) · Nature Reviews Immunology · doi:10.1038/nri3921 · Cited by 1,313
Design of amidobenzimidazole STING receptor agonists with systemic activity
Ramanjulu, J. M., Pesiridis, G. S., Yang, J., Concha, N., Singhaus, R., Zhang, S.-Y., Tran, J.-L., Moore, P., Lehmann, S., Eberl, H. C., et al. (2018) · Nature · doi:10.1038/s41586-018-0705-y · Cited by 912
The cGAS–STING pathway and cancer
Samson, N., & Ablasser, A. (2022) · Nature Cancer · doi:10.1038/s43018-022-00468-w · Cited by 668
The host STING pathway at the interface of cancer and immunity
Corrales, L., McWhirter, S. M., Dubensky, T. W., & Gajewski, T. F. (2016) · Journal of Clinical Investigation · doi:10.1172/jci86892 · Cited by 487
Interferons α and β in cancer: therapeutic opportunities from new insights
Borden, E. C. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-018-0011-2 · Cited by 423
Metadata
- Authors
- Klarquist, J., Hennies, C. M., Lehn, M. A., Reboulet, R. A., Feau, S., & Janssen, E. M.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-12
- Volume
- 193
- Issue
- 12
- Pages
- 6124-6134
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1630358515
- Cited by
- 211
- References
- 11
- FWCI
- 5.71
- Type
- journal article
- Language
- en
- Open access
- green
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- Klarquist, J., Hennies, C. M., Lehn, M. A., Reboulet, R. A., Feau, S., & Janssen, E. M. (2014). STING-Mediated DNA Sensing Promotes Antitumor and Autoimmune Responses to Dying Cells. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1401869
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