title: The Self-Specific Activation Receptor SLAM Family Is Critical for NK Cell Education.
abstract: NK cell education, a term describing a process for NK cell acquisition of functional competence, is primarily achieved by self-MHC-I-specific inhibitory receptors. In this study, we have demonstrated that SLAM family receptors (SFRs) redundantly expressed on hematopoietic cells function as self-specific activation receptors critical for NK cell education. To overcome gene redundancy, we generated mice simultaneously lacking seven SFRs, revealing that NK-cell-mediated rejection of semi-allogeneic hematopoietic cells largely depended on the presence of SFRs on target cells. This stimulatory effect was determined by the presence of SFR-coupled adaptors; however, SFR-deficient mice displayed enhanced reactivity to hematopoietic cells. These findings demonstrate that SFRs endow NK cells with an ability to kill hematopoietic cells during the effector phase; however, the sustained engagement of SFRs can desensitize NK cell responses during an education process. Therefore, self-specific activating ligands may be "tolerogens" for NK cells, akin to self-antigens that induce T cell tolerance.
authors: Institute for Immunology, School of Medicine and Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
authors: Shasha
authors: S
authors: Chen
authors: Biomedical Translational Research Institute, Jinan University, Guangzhou 510632, China.
authors: Meixiang
authors: M
authors: Yang
authors: Institute for Immunology, School of Medicine and Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
authors: Juan
authors: J
authors: Du
authors: Institute for Immunology, School of Medicine and Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
authors: Dan
authors: D
authors: Li
authors: Institute for Immunology, School of Medicine and Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
authors: Zehua
authors: Z
authors: Li
authors: Institute for Immunology, School of Medicine and Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
authors: Chenxu
authors: C
authors: Cai
authors: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Comparative Medical Center, Peking Union Medical College, Beijing 100021, China.
authors: Yuanwu
authors: Y
authors: Ma
authors: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Comparative Medical Center, Peking Union Medical College, Beijing 100021, China.
authors: Lianfeng
authors: L
authors: Zhang
authors: School of Life Sciences, University of Sciences and Technology of China, Hefei 230026, China. Electronic address: tzg@ustc.edu.cn.
authors: Zhigang
authors: Z
authors: Tian
authors: Institute for Immunology, School of Medicine and Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: dongzj@biomed.tsinghua.edu.cn.
authors: Zhongjun
authors: Z
authors: Dong
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D002454:Cell Differentiation; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071176:Signaling Lymphocytic Activation Molecule Family / Q000235:genetics / Q000378:metabolism*; D023001:Transplantation Tolerance
chemical_list: D001324:Autoantigens; D007519:Isoantigens; D000071176:Signaling Lymphocytic Activation Molecule Family