Professional Education


  • Doctor of Philosophy, Tsukuba University (2018)
  • Bachelor of Science, Tsukuba University (2013)

All Publications


  • Cutting Edge: NKG2D Signaling Enhances NK Cell Responses but Alone Is Insufficient To Drive Expansion during Mouse Cytomegalovirus Infection JOURNAL OF IMMUNOLOGY Nabekura, T., Gotthardt, D., Niizuma, K., Trsan, T., Jenus, T., Jonjic, S., Lanier, L. L. 2017; 199 (5): 1567–71

    Abstract

    NK cells play a critical role in host defense against viruses. In this study, we investigated the role of NKG2D in the expansion of NK cells after mouse CMV (MCMV) infection. Wild-type and NKG2D-deficient (Klrk1-/- ) Ly49H+ NK cells proliferated robustly when infected with MCMV strains engineered to allow expression of NKG2D ligands, which enhanced the response of wild-type NK cells. Naive NK cells exclusively express NKG2D-L, which pairs only with DAP10, whereas NKG2D-S expressed by activated NK cells pairs with DAP10 and DAP12, similar to Ly49H. However, NKG2D alone was unable to drive robust expansion of Ly49H- NK cells when mice were infected with these MCMV strains, likely because NKG2D-S was only transiently expressed postinfection. These findings demonstrate that NKG2D augments Ly49H-dependent proliferation of NK cells; however, NKG2D signaling alone is inadequate for expansion of NK cells, likely due to only transient expression of the NKG2D-DAP12 complex.

    View details for DOI 10.4049/jimmunol.1700799

    View details for Web of Science ID 000408005200006

    View details for PubMedID 28760883

    View details for PubMedCentralID PMC5567695

  • Identification and Characterization of CD300H, a New Member of the Human CD300 Immunoreceptor Family JOURNAL OF BIOLOGICAL CHEMISTRY Niizuma, K., Tahara-Hanaoka, S., Noguchi, E., Shibuya, A. 2015; 290 (36): 22298–308

    Abstract

    Recruitment of circulating monocytes and neutrophils to infection sites is essential for host defense against infections. Here, we identified a previously unannotated gene that encodes an immunoglobulin-like receptor, designated CD300H, which is located in the CD300 gene cluster. CD300H has a short cytoplasmic tail and associates with the signaling adaptor proteins, DAP12 and DAP10. CD300H is expressed on CD16(+) monocytes and myeloid dendritic cells. Ligation of CD300H on CD16(+) monocytes and myeloid dendritic cells with anti-CD300H monoclonal antibody induced the production of neutrophil chemoattractants. Interestingly, CD300H expression varied among healthy subjects, who could be classified into two groups according to "positive" and "negative" expression. Genomic sequence analysis revealed a single-nucleotide substitution (rs905709 (G → A)) at a splice donor site on intron 1 on either one or both alleles. The International HapMap Project database has demonstrated that homozygosity for the A allele of single nucleotide polymorphism (SNP) rs905709 ("negative" expression) is highly frequent in Han Chinese in Beijing, Japanese in Tokyo, and Europeans (A/A genotype frequencies 0.349, 0.167, and 0.138, respectively) but extremely rare in Sub-Saharan African populations. Together, these results suggest that CD300H may play an important role in innate immunity, at least in populations that carry the G/G or G/A genotype of CD300H.

    View details for DOI 10.1074/jbc.M115.643361

    View details for Web of Science ID 000360968500045

    View details for PubMedID 26221034

    View details for PubMedCentralID PMC4571981

  • Toll-like receptor 4 and MAIR-II/CLM-4/LMIR2 immunoreceptor regulate VLA-4-mediated inflammatory monocyte migration NATURE COMMUNICATIONS Totsuka, N., Kim, Y., Kanemaru, K., Niizuma, K., Umemoto, E., Nagai, K., Tahara-Hanaoka, S., Nakahasi-Oda, C., Honda, S., Miyasaka, M., Shibuya, K., Shibuya, A. 2014; 5: 4710

    Abstract

    Inflammatory monocytes play an important role in host defense against infections. However, the regulatory mechanisms of transmigration into infected tissue are not yet completely understood. Here we show that mice deficient in MAIR-II (also called CLM-4 or LMIR2) are more susceptible to caecal ligation and puncture (CLP)-induced peritonitis than wild-type (WT) mice. Adoptive transfer of inflammatory monocytes from WT mice, but not from MAIR-II, TLR4 or MyD88-deficient mice, significantly improves survival of MAIR-II-deficient mice after CLP. Migration of inflammatory monocytes into the peritoneal cavity after CLP, which is dependent on VLA-4, is impaired in above mutant and FcRγ chain-deficient mice. Lipopolysaccharide stimulation induces association of MAIR-II with FcRγ chain and Syk, leading to enhancement of VLA-4-mediated adhesion to VCAM-1. These results indicate that activation of MAIR-II/FcRγ chain by TLR4/MyD88-mediated signalling is essential for the transmigration of inflammatory monocytes from the blood to sites of infection mediated by VLA-4.

    View details for DOI 10.1038/ncomms5710

    View details for Web of Science ID 000341078900008

    View details for PubMedID 25134989

    View details for PubMedCentralID PMC4143930