Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses

Foxp3(+) T regulatory (Treg) cells regulate immune responses and maintain self-tolerance. Recent work shows that Treg cells are comprised of many subpopulations with specialized regulatory functions. Here we identified Foxp3(+) T cells expressing the coinhibitory molecule TIGIT as a distinct Treg ce...

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Published in:Immunity (Cambridge, Mass.) Vol. 40; no. 4; p. 569
Main Authors: Joller, Nicole, Lozano, Ester, Burkett, Patrick R, Patel, Bonny, Xiao, Sheng, Zhu, Chen, Xia, Junrong, Tan, Tze G, Sefik, Esen, Yajnik, Vijay, Sharpe, Arlene H, Quintana, Francisco J, Mathis, Diane, Benoist, Christophe, Hafler, David A, Kuchroo, Vijay K
Format: Journal Article
Language:English
Published: United States 17.04.2014
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ISSN:1097-4180, 1097-4180
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Summary:Foxp3(+) T regulatory (Treg) cells regulate immune responses and maintain self-tolerance. Recent work shows that Treg cells are comprised of many subpopulations with specialized regulatory functions. Here we identified Foxp3(+) T cells expressing the coinhibitory molecule TIGIT as a distinct Treg cell subset that specifically suppresses proinflammatory T helper 1 (Th1) and Th17 cell, but not Th2 cell responses. Transcriptional profiling characterized TIGIT(+) Treg cells as an activated Treg cell subset with high expression of Treg signature genes. Ligation of TIGIT on Treg cells induced expression of the effector molecule fibrinogen-like protein 2 (Fgl2), which promoted Treg-cell-mediated suppression of T effector cell proliferation. In addition, Fgl2 was necessary to prevent suppression of Th2 cytokine production in a model of allergic airway inflammation. TIGIT expression therefore identifies a Treg cell subset that demonstrates selectivity for suppression of Th1 and Th17 cell but not Th2 cell responses.
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ISSN:1097-4180
1097-4180
DOI:10.1016/j.immuni.2014.02.012