TY - JOUR
T1 - Contribution of inhibitory receptor TIGIT to NK cell education
AU - He, Yuke
AU - Peng, Hui
AU - Sun, Rui
AU - Wei, Haiming
AU - Ljunggren, Hans Gustaf
AU - Yokoyama, Wayne M.
AU - Tian, Zhigang
N1 - Funding Information:
We thank Dr. Lewis L. Lanier (University of California, San Francisco, USA) for administrative suggestions; Dr. Eric Vivier (Center d'Immunologie de Marseille-Luminy, France) for his provision of Ncr1icre/+ mice; Dr. Zusen Fan (Institute of Biophysics, Chinese Academy of Sciences, China) for sharing Tigitfl/fl mice; Dr. Yoshimi Takai (Kobe University, Japan) and Dr. Stephan Gasser (National University of Singapore, Singapore) for providing Pvr−/- mice; and Bristol-Myers Squibb for providing Tigit−/− mice. This work was supported by the Natural Science Foundation of China (#31390433, 91542114, 81761128013, 81361120388, 31570893, 81571522, 91442112, 91542000) and the Ministry of Science & Technology of China (973 Basic Science Project 2013CB944902, 2013CB530506).
Publisher Copyright:
© 2017
PY - 2017/7
Y1 - 2017/7
N2 - Engagement of inhibitory receptors by cognate host MHC-I molecules triggers NK cell education, resulting in functional maturation and allowing NK cells to sense missing-self. However, NK cells also express inhibitory receptors for non-MHC-I ligands and their role in NK cell education is poorly understood. TIGIT is a recently identified inhibitory receptor that recognizes a non-MHC-I ligand CD155. Here, we demonstrated that TIGIT+ NK cells from wild-type mice exerted augmented responsiveness to various stimuli, including targets that lacked expression of CD155 ligand. TIGIT+ NK cells derived from CD155-deficient hosts, however, exhibited functional impairment, indicating that the engagement of TIGIT receptor by host CD155 promoted NK cell functional maturation. Furthermore, TIGIT deficiency impaired NK cell-mediated missing-self recognition and rejection of CD155- targets, such as allogenic splenocytes and certain tumor cells, in an MHC-I-independent and CD226-unrelated manner. Thus, TIGIT-CD155 pathway is also involved in the acquisition of optimal NK cell effector function, representing a novel MHC-I-independent education mechanism for NK cell tolerance and activation.
AB - Engagement of inhibitory receptors by cognate host MHC-I molecules triggers NK cell education, resulting in functional maturation and allowing NK cells to sense missing-self. However, NK cells also express inhibitory receptors for non-MHC-I ligands and their role in NK cell education is poorly understood. TIGIT is a recently identified inhibitory receptor that recognizes a non-MHC-I ligand CD155. Here, we demonstrated that TIGIT+ NK cells from wild-type mice exerted augmented responsiveness to various stimuli, including targets that lacked expression of CD155 ligand. TIGIT+ NK cells derived from CD155-deficient hosts, however, exhibited functional impairment, indicating that the engagement of TIGIT receptor by host CD155 promoted NK cell functional maturation. Furthermore, TIGIT deficiency impaired NK cell-mediated missing-self recognition and rejection of CD155- targets, such as allogenic splenocytes and certain tumor cells, in an MHC-I-independent and CD226-unrelated manner. Thus, TIGIT-CD155 pathway is also involved in the acquisition of optimal NK cell effector function, representing a novel MHC-I-independent education mechanism for NK cell tolerance and activation.
KW - CD155
KW - Education
KW - Licensing
KW - MHC-I
KW - NK cells
KW - TIGIT
UR - http://www.scopus.com/inward/record.url?scp=85018623508&partnerID=8YFLogxK
U2 - 10.1016/j.jaut.2017.04.001
DO - 10.1016/j.jaut.2017.04.001
M3 - Article
C2 - 28438433
AN - SCOPUS:85018623508
VL - 81
SP - 1
EP - 12
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
SN - 0896-8411
ER -