ArticleJournal of immunology (Baltimore, Md. : 1950)2015
mTOR Complex Signaling through the SEMA4A-Plexin B2 Axis Is Required for Optimal Activation and Differentiation of CD8+ T Cells.
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Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30citing papers in PubMed
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30 citing papers in PubMed, 54 citations in OpenAlex.
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- Current Progress in the Development of mRNA Vaccines Against Bacterial Infections.International journal of molecular sciences · 2024Review
- Unveiling the multifaceted antitumor effects of interleukin 33.Frontiers in immunology · 2024Review
- Tumor-derived semaphorin 4A improves PD-1-blocking antibody efficacy by enhancing CD8Science advances · 2023Article
- Sex differences exist in adult heart group 2 innate lymphoid cells.BMC immunology · 2022Article
- Neural guidance factors as hubs of immunometabolic cross-talk.International immunology · 2021Review
- SLFN2 protection of tRNAs from stress-induced cleavage is essential for T cell-mediated immunity.Science (New York, N.Y.) · 2021Article
- A circular RNA derived from PLXNB2 as a valuable predictor of the prognosis of patients with acute myeloid leukaemia.Journal of translational medicine · 2021Article
- Induced regulatory T cells suppress Tc1 cells through TGF-β signaling to ameliorate STZ-induced type 1 diabetes mellitus.Cellular & molecular immunology · 2021Article
- Semaphorin4A-Plexin D1 Axis Induces Th2 and Th17 While Represses Th1 Skewing in an Autocrine Manner.International journal of molecular sciences · 2020Article
- Neuropilin-1 is a T cell memory checkpoint limiting long-term antitumor immunity.Nature immunology · 2020Article
- mTOR signaling at the crossroads of environmental signals and T-cell fate decisions.Immunological reviews · 2020Review
- Transferrin and H-ferritin involvement in brain iron acquisition during postnatal development: impact of sex and genotype.Journal of neurochemistry · 2020Article
- A Cross-Protective Vaccine Against 4b and 1/2bFrontiers in microbiology · 2020Article
- Induction of Inflammation and Fibrosis by Semaphorin 4A in Systemic Sclerosis.Arthritis & rheumatology (Hoboken, N.J.) · 2019Article
- Semaphorin Signaling in Cancer-Associated Inflammation.International journal of molecular sciences · 2019Review
- Overexpression of Semaphorin-3A and Semaphorin-4D in the Peripheral Blood from Newly Diagnosed Patients with Chronic Lymphocytic Leukemia.International journal of hematology-oncology and stem cell research · 2019Article
- Neuroimmune Semaphorin 4A in Cancer Angiogenesis and Inflammation: A Promoter or a Suppressor?International journal of molecular sciences · 2018Review
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Authors and funding
20 authors at 5 institutions in 1 country.
Daisuke ItoDepartment of Immunopathology, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita City, Osaka 565-0871, Japan; Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan; Department of Respiratory Medicine, Allergy, and Rheumatic Disease, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Suita City, Osaka 565-0871, Japan;
Satoshi NojimaDepartment of Immunopathology, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita City, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Suita City, Osaka 565-0871, Japan; Department of Pathology, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan; s_nojima@molpath.med.osaka-u.ac.jp kumanogo@imed3.med.osaka-u.ac.jp.
Masayuki NishideDepartment of Immunopathology, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita City, Osaka 565-0871, Japan; Department of Respiratory Medicine, Allergy, and Rheumatic Disease, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Suita City, Osaka 565-0871, Japan;
Tatsusada OkunoDepartment of Immunopathology, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita City, Osaka 565-0871, Japan; Department of Neurology, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan;
Hyota TakamatsuDepartment of Immunopathology, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita City, Osaka 565-0871, Japan; Department of Respiratory Medicine, Allergy, and Rheumatic Disease, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Suita City, Osaka 565-0871, Japan;
Sujin KangDepartment of Immunopathology, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita City, Osaka 565-0871, Japan; Department of Respiratory Medicine, Allergy, and Rheumatic Disease, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Suita City, Osaka 565-0871, Japan; Department of Clinical Application of Biologics, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan;
Tetsuya KimuraDepartment of Immunopathology, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita City, Osaka 565-0871, Japan; Department of Respiratory Medicine, Allergy, and Rheumatic Disease, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Suita City, Osaka 565-0871, Japan;
Yuji YoshidaDepartment of Immunopathology, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita City, Osaka 565-0871, Japan; Department of Respiratory Medicine, Allergy, and Rheumatic Disease, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Suita City, Osaka 565-0871, Japan;
Keiko MorimotoDepartment of Immunopathology, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita City, Osaka 565-0871, Japan; Department of Respiratory Medicine, Allergy, and Rheumatic Disease, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Suita City, Osaka 565-0871, Japan;
Yohei MaedaDepartment of Immunopathology, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita City, Osaka 565-0871, Japan; Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan;
Takashi HosokawaDepartment of Immunopathology, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita City, Osaka 565-0871, Japan; Department of Respiratory Medicine, Allergy, and Rheumatic Disease, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Suita City, Osaka 565-0871, Japan;
Toshihiko ToyofukuDepartment of Immunopathology, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita City, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Suita City, Osaka 565-0871, Japan; Department of Immunology and Regenerative Medicine, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan;
Jun OhshimaDepartment of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, Suita City, Osaka 565-0871, Japan; Laboratory of Immunoparasitology, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita City, Osaka 565-0871, Japan; and.
Daisuke KamimuraDepartment of Molecular Neuroimmunology, Institute for Genetic Medicine, Hokkaido University Graduate School of Medicine, Sapporo City, Hokkaido 060-0815, Japan.
Masahiro YamamotoDepartment of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, Suita City, Osaka 565-0871, Japan; Laboratory of Immunoparasitology, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita City, Osaka 565-0871, Japan; and.
Masaaki MurakamiDepartment of Molecular Neuroimmunology, Institute for Genetic Medicine, Hokkaido University Graduate School of Medicine, Sapporo City, Hokkaido 060-0815, Japan.
Eiichi MoriiDepartment of Pathology, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan;
Hiromi RakugiDepartment of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan;
Yoshitaka IsakaDepartment of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan;
Atsushi KumanogohDepartment of Immunopathology, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita City, Osaka 565-0871, Japan; Department of Respiratory Medicine, Allergy, and Rheumatic Disease, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Suita City, Osaka 565-0871, Japan; s_nojima@molpath.med.osaka-u.ac.jp kumanogo@imed3.med.osaka-u.ac.jp.
Osaka City University · JPOsaka International University · JPOsaka University · JPJapan Science and Technology Agency · JPHokkaido University · JP
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mammalian target of rapamycin (mTOR) plays crucial roles in activation and differentiation of diverse types of immune cells. Although several lines of evidence have demonstrated the importance of mTOR-mediated signals in CD4(+) T cell responses, the involvement of mTOR in CD8(+) T cell responses is not fully understood. In this study, we show that a class IV semaphorin, SEMA4A, regulates CD8(+) T cell activation and differentiation through activation of mTOR complex (mTORC) 1. SEMA4A(-/-) CD8(+) T cells exhibited impairments in production of IFN-γ and TNF-α and induction of the effector molecules granzyme B, perforin, and FAS-L. Upon infection with OVA-expressing Listeria monocytogenes, pathogen-specific effector CD8(+) T cell responses were significantly impaired in SEMA4A(-/-) mice. Furthermore, SEMA4A(-/-) CD8(+) T cells exhibited reduced mTORC1 activity and elevated mTORC2 activity, suggesting that SEMA4A is required for optimal activation of mTORC1 in CD8(+) T cells. IFN-γ production and mTORC1 activity in SEMA4A(-/-) CD8(+) T cells were restored by administration of recombinant Sema4A protein. In addition, we show that plexin B2 is a functional receptor of SEMA4A in CD8(+) T cells. Collectively, these results not only demonstrate the role of SEMA4A in CD8(+) T cells, but also reveal a novel link between a semaphorin and mTOR signaling.
Indexed as
AnimalsCD8-Positive T-LymphocytesCell DifferentiationCell ProliferationFas Ligand ProteinGranzymesInterferon-gammaListeria monocytogenesListeriosisLymphocyte ActivationMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2MiceMice, Inbred C57BLMice, KnockoutMultiprotein ComplexesFas Ligand ProteinFasl protein, mouseGranzymesGzmb protein, mouseInterferon-gammaMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2Multiprotein ComplexesNerve Tissue Proteinsperforin, mousePlxnb2 protein, mousePore Forming Cytotoxic ProteinsRecombinant ProteinsRNA, Small InterferingSema4A protein, mouseSemaphorinsTOR Serine-Threonine KinasesTumor Necrosis Factor-alpha
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