Lab Activities

Laboratory for Autoimmune Diseases

Research Activities

Kazuhiko Yamamoto portrait

Team Director

Kazuhiko Yamamoto

Genome-wide association studies (GWAS) are employed to detect genetic variants in diseases and traits involving multiple factors, such as the immune system. Using the information of variants, we are advancing multi-omics analyses of immune cell subsets in healthy individuals (13 at steady state, 7 upon stimulation) to elucidate the mechanisms of the human immune system. Particular attention is paid to subset-specific chromatin accessibility QTLs(caQTLs) and eQTLs concerning genetic risk variants, noting that many colocalize with transcription factor binding sites, enhancers, and promoters in non-coding regions. Analyses employ not only ATAC-seq and histone modifications for caQTL detection, but also ReapTEC (Oguchi A et al. Science 2024) for the precise measurement of 5'-end RNA sequences. Furthermore, subset-specific proteome, lipidome, and metabolome analyses are being conducted as intermediate traits closer to the final phenotypes. Additionally, incorporating gut and saliva microbiota as an environmental factor and the metabolome as effector molecules produced by these bacteria, the ultimate goal is to construct a dataset of 400 individuals. Data analysis employs statistical genetics aimed at elucidating mechanisms and causality, alongside AI analysis to enhance functional prediction. Utilizing this constructed dataset is expected to significantly advance research into the mechanisms of the human immune system.

These studies are based on the collaborative works of about ten teams at IMS with a grant of AMED SCARDA. Our team, one of the core teams, is responsible for collecting samples of immune cells and microbiomes from healthy individuals and vaccine recipients, isolating and stimulating immune cell subsets, and performing genomic, epigenomic, and gene expression analyses. We also provide samples of lymphocyte subsets to teams in charge of proteomics, lipidomics, and metabolomics, and supply measurement data to teams in charge of data processing and analysis.

Multi-omics approach to understanding the human immune system

Laboratory for Autoimmune Diseases figure

Multi-omics approach to understanding the human immune system

Laboratory for Autoimmune Diseases figure

Peripheral blood is collected from healthy individuals, separated into various immune cell subsets in steady-state alongside with each major subset cultured in a specific stimulation condition. Comprehensive analyses encompass RNA, protein, lipid, and metabolite profiling across all 20 subsets, together with genomic data, gut and oral microbiome studies, and cytokine assessments.

Peripheral blood is collected from healthy individuals, separated into various immune cell subsets in steady-state alongside with each major subset cultured in a specific stimulation condition. Comprehensive analyses encompass RNA, protein, lipid, and metabolite profiling across all 20 subsets, together with genomic data, gut and oral microbiome studies, and cytokine assessments.

Recent Major Publications

  1. Koide R, Abe T, Harimoto T, Kamada  AJ, Saito Y, Guerrini  M, Fujii A, Parrish E, Horie  M, Kiyonari H, Yamamoto  K, Tomonaga K, Parrish  NF. Interferon and TLR genes, but not endogenous bornavirus-like elements, limit BoDV1 replication after intracerebral infection. PLoS Pathog 21, e1013165 (2025)

  2. Izuka S, Komai T, Itamiya T, Ota M, Yamada S, Nagafuchi Y, Shoda H, Matsuki K, Yamamoto K, Okamura T, Fujio K. Integration of transcriptome and immunophenotyping data highlights differences in the pathogenetic kinetics of B cells across immune-mediated disease. RMD Open 11, e0053310 (2025)

  3. Yamamoto K. How to analyze and understand the human immune system. Semin Arthritis Rheum 72S, 152696 (2025)

  4. Akutsu Y, Ota M, Itamiya T, Mori M, Morio T, Yamamoto K, Okamura T, Fujio K. Effect of Epstein-Barr Virus infection on gene regulation in immune cells of patients with Immune-Mediated Diseases. J Autoimmun 150, 103355 (2025)

  5. Natsumoto B, Shoda H, Tsuji M, Otsu M, Taniguchi H, Yamamoto K, Fujio K. Identification of Potential Therapeutic Agents for Type I Interferonopathy Using iPSC-Based Disease Modeling. J Clin Immunol 45, 140 (2025)

  6. Kock K, Tan L, Han K, Ando Y, Jevapatarakul D, Chatterjee A, Lin Q, Buyamin E, Sonthalia R, Rajagopalan D, Tomofuji Y, Sankaran S, Park M, Abe M, Chantaraamporn J, Furukawa S, Ghosh S, Inoue G, Kojima M, Kouno T, Lim J, Myouzen K, Nguantad S, Oh J, Rayan N, Sarkar S, Suzuki A, Thungsatianpun N, Venkatesh P, Moody J, Nakano M, Chen Z, Tian C, Zhang Y, Tong Y, Tan C, Tizazu A, Loh M, Hwang Y, Ho RC, Larbi A, Ng T, Won H, Wright FA, Villani A, Park J, Choi M, Liu B, Maitra A, Pithukpakorn M, Suktitipat B, Ishigaki K, Okada Y, Yamamoto K, Carninci P, Chambers JC, Hon C, Matangkasombut P, Charoensawan V, Majumder PP, Shin JW, Park W, Prabhakar S. Asian diversity in human immune cells. Cell 188, 2288-2306.e24 (2025)

  7. Sasa N, Kojima S, Koide R, Hasegawa T, Namkoong H, Hirota T, Watanabe R, Nakamura Y, Oguro-Igashira E, Ogawa K, Yata T, Sonehara K, Yamamoto K, Kishikawa T, Sakaue S, Edahiro R, Shirai Y, Maeda Y, Nii T, Chubachi S, Tanaka H, Yabukami H, Suzuki A, Nakajima K, Arase N, Okamoto T, Nishikawa R, Namba S, Naito T, ..., Kanai T, Morita A, Matsuda F, Tamari M, Kumanogoh A, Tanaka Y, Ohmura K, Fukunaga K, Imoto S, Miyano S, Parrish NF, Okada Y. Blood DNA virome associates with autoimmune diseases and COVID-19. Nat Genet 57, 65–79 (2025)

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