TIGIT predominantly regulates the immune response via regulatory T cells

Kurtulus, Sema, Sakuishi, Kaori, Ngiow, Shin-Foong, Joller, Nicole, Tan, Dewar J., Teng, Michele W. L., Smyth, Mark J., Kuchroo, Vijay K. and Anderson, Ana C. (2015) TIGIT predominantly regulates the immune response via regulatory T cells. Journal of Clinical Investigation, 125 11: 4053-4062. doi:10.1172/JCI81187


Author Kurtulus, Sema
Sakuishi, Kaori
Ngiow, Shin-Foong
Joller, Nicole
Tan, Dewar J.
Teng, Michele W. L.
Smyth, Mark J.
Kuchroo, Vijay K.
Anderson, Ana C.
Title TIGIT predominantly regulates the immune response via regulatory T cells
Journal name Journal of Clinical Investigation   Check publisher's open access policy
ISSN 0021-9738
1558-8238
Publication date 2015-11-02
Year available 2015
Sub-type Article (original research)
DOI 10.1172/JCI81187
Open Access Status DOI
Volume 125
Issue 11
Start page 4053
End page 4062
Total pages 10
Place of publication Ann Arbor, MI United States
Publisher American Society for Clinical Investigation
Language eng
Formatted abstract
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
 
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