The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
TIGIT predominantly regulates the immune response via regulatory T cells
Open accessAbstract
Coinhibitory receptors are critical for the maintenance of immune homeostasis. Upregulation of these receptors on effector T cells terminates T cell responses, while their expression on Tregs promotes their suppressor function. Understanding the function of coinhibitory receptors in effector T cells and Tregs is crucial, as therapies that target coinhibitory receptors are currently at the forefront of treatment strategies for cancer and other chronic diseases. T cell Ig and ITIM domain (TIGIT) is a recently identified coinhibitory receptor that is found on the surface of a variety of lymphoid cells, and its role in immune regulation is just beginning to be elucidated. We examined TIGIT-mediated immune regulation in different murine cancer models and determined that TIGIT marks the most dysfunctional subset of CD8+ T cells in tumor tissue as well as tumor-tissue Tregs with a highly active and suppressive phenotype. We demonstrated that TIGIT signaling in Tregs directs their phenotype and that TIGIT primarily suppresses antitumor immunity via Tregs and not CD8+ T cells. Moreover, TIGIT+ Tregs upregulated expression of the coinhibitory receptor TIM-3 in tumor tissue, and TIM-3 and TIGIT synergized to suppress antitumor immune responses. Our findings provide mechanistic insight into how TIGIT regulates immune responses in chronic disease settings.
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Cites
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“In chronic diseases, the dysregulated expression of coinhibitory receptors on effector T cells is associated with a dysfunctional effector phenotype characterized by deficits in proliferative capacity, secretion of proinflammatory cytokines, and cytotoxicity (1).”
BackgroundThe interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity
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Cited by
Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation
Anderson, A. C., Joller, N., & Kuchroo, V. K. (2016) · Immunity · doi:10.1016/j.immuni.2016.05.001 · Cited by 2,096
Self-citationNovel immune checkpoint targets: moving beyond PD-1 and CTLA-4
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Metadata
- Authors
- Kurtulus, S., Sakuishi, K., Ngiow, S.-F., Joller, N., Tan, D. J., Teng, M. W. L., Smyth, M. J., Kuchroo, V. K., & Anderson, A. C.
- Venue
- Journal of Clinical Investigation
- Published
- 2015-09-28
- Volume
- 125
- Issue
- 11
- Pages
- 4053-4062
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- OpenAlex
- W2142169541
- Cited by
- 551
- References
- 13
- FWCI
- 14.43
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- bronze
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- Kurtulus, S., Sakuishi, K., Ngiow, S.-F., Joller, N., Tan, D. J., Teng, M. W. L., Smyth, M. J., Kuchroo, V. K., & Anderson, A. C. (2015). TIGIT predominantly regulates the immune response via regulatory T cells. Journal of Clinical Investigation. https://doi.org/10.1172/jci81187
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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