title: The Secreted Form of Transmembrane Protein 98 Promotes the Differentiation of T Helper 1 Cells.
abstract: Cytokines mediate the interaction of immune cells. Discovery of novel potential cytokines is of great value for both basic research and clinical application. In this study, we identified a novel immune-related molecule, transmembrane protein 98 (TMEM98), through a high-throughput screening platform for novel potential cytokines at a genome-wide level using the strategy of immunogenomics. So far, there is no characteristic and immune-related functional report about it. In this study, we demonstrate that TMEM98 exists as a type II transmembrane protein both in the ectopically and endogenously expressed systems. Interestingly, TMEM98 could also be secreted through exosomes. Moreover, the native secreted form of TMEM98 could be detected in the supernatants of activated human peripheral blood mononuclear cells and mouse CD4(+) T cells. Further expression profile analysis showed TMEM98 was upregulated during the activation and differentiation of T helper (Th) 1 cells. Function analysis showed that eukaryotic recombinant TMEM98 (rTMEM98) promoted the differentiation of Th1 cells under both antigen-nonspecific and antigen-specific Th1-skewing conditions. These findings were further confirmed in vivo as prokaryotic rTMEM98 administration significantly increased antigen-specific IFN-γ production and serum antigen-specific IgG2a in the methylated bovine serum albumin-induced delayed-type hypersensitivity model. Overall, these observations emphasize the characteristics and essential roles of TMEM98 for the first time and will be helpful in further understanding the development of Th1 cells.
authors.affiliation: 1 Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center , Beijing, China .|2 Peking University Center for Human Disease Genomics , Beijing, China .|3 Tsinghua University School of Medicine , Beijing, China .
authors.forename: Weiwei
authors.initials: W
authors.lastname: Fu
authors.affiliation: 1 Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center , Beijing, China .|2 Peking University Center for Human Disease Genomics , Beijing, China .
authors.forename: Yingying
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: 1 Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center , Beijing, China .|2 Peking University Center for Human Disease Genomics , Beijing, China .
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1 Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center , Beijing, China .|2 Peking University Center for Human Disease Genomics , Beijing, China .
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Mo
authors.affiliation: 1 Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center , Beijing, China .|2 Peking University Center for Human Disease Genomics , Beijing, China .
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: 1 Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center , Beijing, China .
authors.forename: Yuanfeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 1 Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center , Beijing, China .|2 Peking University Center for Human Disease Genomics , Beijing, China .
authors.forename: Pingzhang
authors.initials: P
authors.lastname: Wang
authors.affiliation: 1 Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center , Beijing, China .|2 Peking University Center for Human Disease Genomics , Beijing, China .
authors.forename: Wen
authors.initials: W
authors.lastname: Pan
authors.affiliation: 1 Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center , Beijing, China .|2 Peking University Center for Human Disease Genomics , Beijing, China .
authors.forename: Yingyu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 1 Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center , Beijing, China .
authors.forename: Yintong
authors.initials: Y
authors.lastname: Xue
authors.affiliation: 1 Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center , Beijing, China .|2 Peking University Center for Human Disease Genomics , Beijing, China .
authors.forename: Dalong
authors.initials: D
authors.lastname: Ma
authors.affiliation: 1 Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center , Beijing, China .
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1 Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center , Beijing, China .|2 Peking University Center for Human Disease Genomics , Beijing, China .
authors.forename: Wenling
authors.initials: W
authors.lastname: Han
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D008565:Membrane Proteins; D007371:Interferon-gamma