title: TIGIT expression levels on human NK cells correlate with functional heterogeneity among healthy individuals.
abstract: Human NK cells display extensive phenotypic and functional heterogeneity among healthy individuals, but the mechanism responsible for this variation is still largely unknown. Here, we show that a novel immune receptor, T-cell immunoglobulin and ITIM domain (TIGIT), is expressed preferentially on human NK cells but shows wide variation in its expression levels among healthy individuals. We found that the TIGIT expression level is related to the phenotypic and functional heterogeneity of NK cells, and that NK cells from healthy individuals can be divided into three categories according to TIGIT expression. NK cells with low levels of TIGIT expression show higher cytokine secretion capability, degranulation activity, and cytotoxic potential than NK cells with high levels of TIGIT expression. Blockade of the TIGIT pathway significantly increased NK-cell function, particularly in NK cells with high levels of TIGIT expression. We further observed that the TIGIT expression level was inversely correlated with the IFN-γ secretion capability of NK cells in patients with cancers and autoimmune diseases. Importantly, we propose a novel mechanism that links TIGIT expression with NK-cell functional heterogeneity, and this mechanism might partially explain why individuals have different susceptibilities to infection, autoimmune disease, and cancer.
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Hou
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shiji
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Weiyong
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Botao
authors.initials: B
authors.lastname: Yin
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Lie
authors.initials: L
authors.lastname: Mao
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ziyong
authors.initials: Z
authors.lastname: Sun
mesh_terms: D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008297:Male; D011971:Receptors, Immunologic / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: C573415:IFNG protein, human; D011971:Receptors, Immunologic; C534712:TIGIT protein, human; D007371:Interferon-gamma
keywords: Cytokine secretion; Cytotoxity; Human; NK cells; TIGIT