title: Tim-3 pathway affects NK cell impairment in patients with active tuberculosis.
abstract: Active tuberculosis (TB) patients show impaired NK cell function, and the underlying mechanism remains largely unknown. In this study, we confirmed the decrease in activation, cytokine secretion, and degranulation potential of NK cells in active TB patients. We further investigated whether coinhibitory receptor Tim-3 was involved with impairment of NK cells. Our results revealed that the expression of Tim-3 on NK cells was increased in active TB patients. Tim-3 expression was inversely correlated with IL-12-stimualted IFN-γ production. Moreover, blocking the Tim-3 pathway restored IFN-γ secretion and degranulation of NK cells. Blocking this pathway also increased NK cell cytotoxicity against K562 target cells, and improved the ability of NK cells to control Mtb growth in monocyte-derived macrophages. The Tim-3 expression on NK cells was also observed to be significantly decreased in TB patients post-treatment. In this study, we have identified that Tim-3 is involved with NK cell impairment in TB patients.
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: fengwang@tjh.tjmu.edu.cn.
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. Electronic address: houhongyan89@163.com.
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. Electronic address: wilson547@163.com.
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. Electronic address: tangqingmed@163.com.
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. Electronic address: huangminry2013@163.com.
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. Electronic address: 813713911@qq.com.
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. Electronic address: 1256922951@qq.com.
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. Electronic address: weiyongliu@gmail.com.
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. Electronic address: 284022985@qq.com.
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. Electronic address: lucomeon@126.com.
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. Electronic address: zysun@tjh.tjmu.edu.cn.
authors.forename: Ziyong
authors.initials: Z
authors.lastname: Sun
mesh_terms: D015550:Cell Degranulation; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000254:growth & development; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*
chemical_list: C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: NK cells; Tim-3; Tuberculosis