{"id":"hum0214","version":4,"url":"https://humandbs.dbcls.jp/research/hum0214/v4","datePublished":"2022-01-21","versions":[{"version":1,"datePublished":"2020-10-09"},{"version":2,"datePublished":"2021-03-05"},{"version":3,"datePublished":"2021-04-28"},{"version":4,"datePublished":"2022-01-21"},{"version":5,"datePublished":"2022-03-09"},{"version":6,"datePublished":"2022-08-25"},{"version":7,"datePublished":"2023-03-28"},{"version":8,"datePublished":"2023-07-06"},{"version":9,"datePublished":"2024-02-08"},{"version":10,"datePublished":"2026-06-09"}],"title":{"ja":"ヒト免疫系の機能ゲノム学による統合的理解とこれを用いた免疫疾患の発症予防のためのインターベンション戦略の構築","en":"Integrative understanding of human immune system by functional genomics and development of intervention strategies for the prevention of autoimmune diseases"},"summary":{"aims":{"ja":"免疫細胞における遺伝子発現制御と免疫疾患に対する寄与を解明する","en":"To elucidate the regulation of gene expression in each immune cell subset and its contribution to autoimmune diseases."},"methods":{"ja":"JGAS000220（JGAD000309、JGAD000310）：全身性強皮症21症例、antineutrophil cytoplasmic antibody（ANCA）関連血管炎26症例、対照健常者28名の末梢血免疫細胞画分を分取し各画分から抽出したtotal RNAを用いたRNA-seqを実施した。\nE-GEAD-397 / E-GEAD-398 / E-GEAD-420：全身性エリテマトーデス、筋炎、全身性強皮症、混合性結合組織病、シェーグレン症候群、関節リウマチ、ベーチェット病、成人スチル病、ANCA関連血管炎、高安動脈炎、対照健常者の全血及び末梢血免疫細胞28画分を分取し、全血より全ゲノムシーケンス、各画分サンプルを用いてRNA-seqを実施した。サンプルのフィルタリングと遺伝子発現量の標準化の上で、各免疫細胞画分でeQTL解析を実施した。\nJGAS000296：全身性強皮症50症例、対照健常者48名の末梢血免疫細胞24画分を分取し、各画分サンプルを用いてRNA-seqを実施した。遺伝子発現量を定量し、サンプルのフィルタリングを行った。\nJGAS000220（JGAD000371、JGAD000372、JGAD000373）：全身性エリテマトーデス、対照健常者の末梢血免疫細胞19画分を分取し、各画分サンプルを用いてRNA-seqを実施した。末梢血免疫細胞15画分でATAC-seqを実施した。\nJGAS000486：全身性エリテマトーデス、対照健常者の末梢血免疫細胞27画分を分取し、各画分サンプルを用いてRNA-seqを実施した。\nJGAS000598：関節リウマチ50症例、対照健常者39名の末梢血免疫細胞18画分を分取し、各画分サンプルを用いてRNA-seqを実施した。関節リウマチ15症例については、経時的な解析を実施した。\nJGAS000485：全身性エリテマトーデス、全身性強皮症、筋炎、混合性結合組織病、シェーグレン症候群、関節リウマチ、ベーチェット病、成人スチル病、ANCA関連血管炎、高安動脈炎、対照健常者の末梢血B細胞5画分を分取した。各画分サンプルを用いてRNA-seqを実施し、B細胞受容体配列のマッピングを実施した。\nJGAS000626：関節リウマチ19症例、全身性エリテマトーデス62症例、特発性炎症性筋疾患40症例、対照健常者64名の末梢血免疫細胞9画分を分取し、各画分サンプルを用いてRNA-seqを実施した。遺伝子発現量を定量し、サンプルのフィルタリングを行った。\nJGAS000627：全身性エリテマトーデス136症例、対照健常者89名の末梢血免疫細胞27画分を分取し、各画分サンプルを用いてRNA-seqを実施した。遺伝子発現量を定量し、サンプルのフィルタリングを行った。\nJGAS000648：炎症性筋疾患6症例、対照健常者1名から末梢血・筋組織・気管支洗浄液を採取した。末梢血についてはCD4T細胞を分取し、scRNA-seqを実施し遺伝子発現量を定量した。筋組織・気管支洗浄液についてはCD45陽性細胞を分取し、scRNA-seqを実施し遺伝子発現量を定量した上でCD4Tクラスターに属する細胞のみを抽出した。","en":"JGAS000220 (JGAD000309, JGAD000310): Various immune cell subsets from 21 systemic sclerosis patients, 26 ANCA associated vasculitis, and 28 healthy controls were collected (Naive_B, SM_B, USM_B, DN_B, Plasmablast, Th1, Th2, Th17, Tfh, Naive_CD4, Mem_CD4, Fr._II_eTreg, Naive_CD8, Mem_CD8, mDC, pDC, CD16p_Mono, CD16n_Mono, NK, Neu) and total RNAs were extracted from each subset. RNA-seq was performed for each sample.\nE-GEAD-397 / E-GEAD-398 / E-GEAD-420: Whole blood and 28 immune cell subsets from study population were collected (Naive_CD4, Mem_CD4, Fr._I_nTreg, Fr._II_eTreg, Fr._III_T, Th1, Th2, Th17, Tfh, NK, Naive_CD8, Mem_CD8, EM_CD8, CM_CD8, TEMRA_CD8, Naive_B, USM_B, SM_B, DN_B, Plasmablast, CL_Mono (or CD16n_Mono), CD16p_Mono, Int_Mono, NC_Mono, mDC, pDC, LDG, Neu). Whole genome sequencing was performed with whole blood samples. RNA-seq was performed with each immune cell subset samples. After filtering and normalization of the gene expression data, eQTL analysis was performed in each immune cell type.\nJGAS000296: 24 peripheral blood immune cell subsets from 50 systemic sclerosis patients and 48 healthy controls were collected (Naive_CD4, Mem_CD4, Fr._I_nTreg, Fr._II_eTreg, Fr._III_T, Th1, Th2, Th17, Tfh, NK, Naive_CD8, EM_CD8, CM_CD8, TEMRA_CD8, Naive_B, USM_B, SM_B, DN_B, Plasmablast, CL_Mono, Int_Mono, NC_Mono, mDC, pDC). RNA-seq was performed with each immune cell subset samples. After gene expression quantification samples were filtered.\nJGAS000220 (JGAD000371, JGAD000372, JGAD000373): 19 immune cell subsets from study population were collected (Naive_CD4, Mem_CD4, Fr._II_eTreg, Th1, Th2, Th17, Tfh, NK, Naive_CD8, Mem_CD8, Naive_B, USM_B, SM_B, DN_B, Plasmablast, CD16n_Mono, CD16p_Mono, mDC, pDC). RNA-seq was performed with each immune cell subset sample. ATAC-seq of 15 immune cell subsets was also performed.\nJGAS000486: Various peripheral blood immune cell subsets from 89 healthy volunteers and 136 systemic lupus erhythematosus (SLE) donors were collected (Naive_CD4, Mem_CD4, Th1, Th2, Th17, Tfh, Fr._I_nTreg, Fr._II_eTreg, Fr._III_T, Naive_CD8, EM_CD8, CM_CD8, TEMRA_CD8, NK, Naive_B, USM_B, SM_B, DN_B, Plasmablast, CL_Mono (or CD16n_Mono), CD16p_Mono, Int_Mono, NC_Mono, mDC, pDC, Neu, LDG). 22 SLE patients were analyzed longitudinally. RNA-seq was performed with each immune cell subset samples. After gene expression quantification samples were filtered.\nJGAS000598: Various peripheral blood immune cell subsets from 39 healthy volunteers and 50 rheumatoid (RA) donors were collected (CD16p_Mono, CL_Mono, DN_B, Fr_II_eTreg, mDC, Mem_CD4, Naive_B, Naive_CD4, Neu, NK, pDC, Plasmablast, SM_B, Tfh, Th1, Th17, Th2, USM_B). 15 RA patients were analyzed longitudinally. RNA-seq was performed with each immune cell subset samples. After gene expression quantification samples were filtered.\nJGAS000485: Peripheral blood B cell subsets from study population were collected (Naive_B, USM_B, SM_B, DN_B, Plasmablast). RNA-seq was performed with each B cell subset samples. B cell receptor sequences were aligned.\nJGAS000626: 9 immune cell subsets from study population were collected (Naive_CD4, Th1, Th2, Th17, Tfh, Fr._I_nTreg, Fr._II_eTreg, Fr._III_T, ThA). RNA-seq was performed with each immune cell subset samples. After gene expression quantification samples were filtered.\nJGAS000627: 27 immune cell subsets from study population were collected (Naive_CD4, Th1, Th2, Th17, Tfh, Fr._I_nTreg, Fr._II_eTreg, Fr._III_T, ThA, Naive_CD8, Naive_B, SM_B, USM_B, DN_B, Plasmablast, NK, CD16p_Mono, CL_Mono, Neu, mDC, pDC, TEMRA_CD8, CM_CD8, EM_CD8, NC_Mono, Int_Mono, LDG). RNA-seq was performed with each immune cell subset samples. After gene expression quantification samples were filtered.\nJGAS000648: Peripheral blood, muscle tissue, and bronchial lavage fluid were collected from each subject. For peripheral blood, CD4T cells were collected and scRNA-seq was performed to quantify gene expression. For muscle tissue and bronchial lavage fluid, CD45-positive cells were collected, scRNA-seq was performed, gene expression was quantified, and CD4T cluster was selected."},"targets":{"ja":"全身性強皮症、全身性エリテマトーデス、筋炎、混合性結合組織病、シェーグレン症候群、関節リウマチ、ベーチェット病、成人スチル病、ANCA関連血管炎、高安動脈炎、対照健常者","en":"Systemic Sclerosis, Systemic Lupus Erythematosus, Myositis, Mixed Connective Tissue Disease, Sjögren's Syndrome, Rheumatoid Arthritis, Behçet's Disease, Adult Onset Still's Disease, ANCA-associated Vasculitis, Takayasu's Arteritis, healthy individuals"},"url":{"ja":[{"url":"https://ryumachi.umin.jp/","text":"https://ryumachi.umin.jp/"}],"en":[{"url":"https://www.h.u-tokyo.ac.jp/english/centers-services/clinical-divisions/allergy-and-rheumatology/index.html","text":"https://www.h.u-tokyo.ac.jp/english/centers-services/clinical-divisions/allergy-and-rheumatology/index.html"}]}},"listingSummary":{},"releaseNote":{"ja":"全身性強皮症50症例、対照健常者48名の末梢血免疫細胞24画分を分取し、各画分から抽出したRNAを用いたRNA-seqを実施した。解析した際の各遺伝子にマップされたリード数を提供する（txt）。","en":"RNAs extracted from 24 immune cell subsets of 50 systemic sclerosis patients and 48 healthy controls were collected. RNA-seq was performed for each sample. Read count data mapped to each gene are provided as txt files."},"dataProviders":[{"name":{"ja":"藤尾 圭志","en":"Keishi Fujio"},"organization":{"name":{"ja":"東京大学大学院 医学系研究科 アレルギー・リウマチ学","en":"Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo"}}}],"researchProjects":[{"name":{"ja":"免疫疾患の免疫細胞マルチオミクス解析","en":"Immune cell multi-omics analysis of immune-mediated diseases"},"url":{"ja":[{"url":"https://ryumachi.umin.jp/","text":"https://ryumachi.umin.jp/"}],"en":[{"url":"https://www.h.u-tokyo.ac.jp/english/centers-services/clinical-divisions/allergy-and-rheumatology/index.html","text":"https://www.h.u-tokyo.ac.jp/english/centers-services/clinical-divisions/allergy-and-rheumatology/index.html"}]}}],"grants":[{"title":{"ja":"ゲノムおよび遺伝子発現情報の統合的解析に基づく全身性エリテマトーデスの治療標的の同定とその制御法の開発","en":"Identification of therapeutic targets and development of intervention strategy for systemic lupus erythematosus based on the comprehensive analysis of genome and transcriptome."},"agency":{"ja":"日本医療研究開発機構（AMED） 難治性疾患実用化研究事業","en":"Practical Research Project for Rare / Intractable Diseases, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP17ek0109103"]},{"title":{"ja":"免疫担当細胞eQTLデータを用いた免疫介在性疾患ゲノム情報からの層別化および予後予測モデルの構築","en":"Construction of stratification and prognosis prediction models from immune-mediated disease genomic information using immune cell eQTL data"},"agency":{"ja":"日本医療研究開発機構（AMED） ゲノム医療実現バイオバンク利活用プログラム","en":"Platform Program for Promotion of Genome Medicine, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP21tm0424221"]},{"title":{"ja":"病気につながる血管周囲の微小炎症を標的とする量子技術、ニューロモデュレーション医療による未病時治療法の開発","en":"Quantum and neuron modulation technologies to suppress tissue-specific disease-related microinflammation"},"agency":{"ja":"日本医療研究開発機構（AMED） 健康・医療分野におけるムーンショット型研究開発等事業","en":"Moonshot Research and Development Program, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP21zf0127004"]},{"title":{"ja":"自己免疫性疾患の臓器病変局所におけるシングルセルRNAシークエンスを用いたマルチオミックス解析による病態解明基盤の構築","en":"Integrative multi-omics analysis of autoimmune diseases based on single cell RNA-sequencing of inflammatory organs"},"agency":{"ja":"日本医療研究開発機構（AMED）免疫アレルギー疾患実用化研究事業","en":"Practical Research Project for Allergic Diseases and Immunology, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP22ek0410074"]},{"title":{"ja":"自己免疫疾患における細胞傷害応答と適応免疫応答双方の免疫記憶に関連するT細胞サブセットの解明","en":"Study of T cell subsets associated with immune memory for both cytotoxic and adaptive immune responses in autoimmune diseases"},"agency":{"ja":"国立研究開発法人日本医療研究開発機構（AMED） 革新的先端研究開発支援事業","en":"Advanced Research and Development Programs for Medical Innovation , Japan Agency for Medical Research and Development (AMED-CREST)"},"grantIds":["JP23gm1810005"]},{"title":{"ja":"マルチオームシングルセル解析を用いた自己免疫疾患における加齢関連T細胞の機能解析","en":"Single-cell multiome profiling and functional analysis of human age-associated T cells in autoimmune diseases"},"agency":{"ja":"科学研究費助成事業 基盤研究（B）","en":"KAKENHI Grant-in-Aid for Scientific Research (B)"},"grantIds":["22H03110"]},{"title":{"ja":null,"en":null},"agency":{"ja":"中外製薬株式会社との共同研究費","en":"Collaborative research fund with Chugai Pharmaceutical Co., Ltd."},"grantIds":null}],"relatedPublications":[{"title":"Integrated bulk and single-cell RNA-sequencing identified disease-relevant monocytes and a gene network module underlying systemic sclerosis","doi":"https://doi.org/10.1016/j.jaut.2020.102547","datasets":["JGAD000309","E-GEAD-344"]},{"title":"Identifying the most influential gene expression profile in distinguishing ANCA-associated vasculitis from healthy controls","doi":"https://doi.org/10.1016/j.jaut.2021.102617","datasets":["JGAD000310"]},{"title":"Dynamic landscape of immune cell-specific gene regulation in immune-mediated diseases","doi":"https://doi.org/10.1016/j.cell.2021.03.056","datasets":["E-GEAD-397","E-GEAD-398","E-GEAD-420"]},{"title":"Dysregulation of the gene signature of effector regulatory T cells in the early phase of systemic sclerosis","doi":"https://doi.org/10.1093/rheumatology/keac031","datasets":["JGAD000406"]},{"title":"Immune cell multiomics analysis reveals contribution of oxidative phosphorylation to B-cell functions and organ damage of lupus","doi":"https://doi.org/10.1136/annrheumdis-2021-221464","datasets":["JGAD000371","JGAD000372","JGAD000373"]},{"title":"Distinct transcriptome architectures underlying lupus establishment and exacerbation","doi":"https://doi.org/10.1016/j.cell.2022.07.021","datasets":["JGAD000603"]},{"title":"Immunomics analysis of rheumatoid arthritis identified precursor dendritic cells as a key cell subset of treatment resistance","doi":"https://doi.org/10.1136/ard-2022-223645","datasets":["JGAD000727","JGAD000731"]},{"title":"Multimodal repertoire analysis unveils B cell biology in immune-mediated diseases","doi":"https://doi.org/10.1136/ard-2023-224421","datasets":["JGAD000602"]},{"title":"Age-associated CD4+ T cells with B cell-promoting functions are regulated by ZEB2 in autoimmunity","doi":"https://doi.org/10.1126/sciimmunol.adk1643","datasets":["JGAD000755","JGAD000756","JGAD000778"]}],"datasets":["JGAD000309","JGAD000310","JGAD000371","JGAD000372","JGAD000373","E-GEAD-397","E-GEAD-398","E-GEAD-420","JGAD000406"],"controlledAccessUsers":[{"principalInvestigator":{"ja":"浜田 道昭","en":"Michiaki Hamada"},"affiliation":{"ja":"浜田研究室, 理工学術院, 早稲田大学","en":"Hamada Laboratory, Faculty of Science and Engineering, Waseda University"},"country":{"ja":"日本","en":"Japan"},"researchTitle":{"ja":"RNA標的創薬データベースの構築","en":"Construction of RNA-targeted Drug Discovery Database"},"periodStart":"2023-01-05","periodEnd":"2027-10-31","datasets":["JGAD000309","JGAD000310","JGAD000371","JGAD000372","JGAD000373","JGAD000406","JGAD000602","JGAD000603","JGAD000727","JGAD000755","JGAD000756","JGAD000778"]},{"principalInvestigator":{"en":"Ana Rita Grosso"},"affiliation":{"en":"Computational Multi-Omics Lab, Department of Life Sciences, Universidade Nova de Lisboa - NOVA School of Science and Technology"},"country":{"ja":"ポルトガル","en":"Portugal"},"researchTitle":{"en":"Assessing transcriptional dyregulation of repetitive elements and monoallelic-expressed genes in lupus"},"periodStart":"2023-04-25","periodEnd":"2026-04-10","datasets":["JGAD000603"]},{"principalInvestigator":{"en":"jiucun wang"},"affiliation":{"en":"jiu-cunwang lab , jiu-cun wang , department of anthropology and human genetics, department of anthropology and human genetics of fudan university"},"country":{"ja":"中国","en":"China"},"researchTitle":{"en":"The role and mechanism study of glycosyltransferase-B3GNT2 in regulating macrophages of Ankylosing Spondylitis"},"periodStart":"2023-03-08","periodEnd":"2024-03-01","datasets":["JGAD000309","JGAD000603"]},{"principalInvestigator":{"en":"Jacob Jaffe"},"affiliation":{"en":"Data Science, Odyssey Therapeutics"},"country":{"ja":"アメリカ合衆国 (マサチューセッツ州)","en":"Massachusetts, United States"},"researchTitle":{"en":"Investigation of immune cell transition states in autoimmune disease"},"periodStart":"2023-04-06","periodEnd":"2023-11-02","datasets":["JGAD000309","JGAD000371","JGAD000372","JGAD000603"]},{"principalInvestigator":{"ja":"武田 吉人","en":"yoshito takeda"},"affiliation":{"ja":"大学院医学系研究科　呼吸器免疫内科学, 大阪大学","en":"Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University"},"country":{"ja":"日本","en":"Japan"},"researchTitle":{"ja":"呼吸器系・免疫疾患における細胞外小胞に着目した病態解明および診断法の開発","en":"Pathophysiology and diagnostic development with a focus on extracellular vesicles in respiratory and immunological diseases"},"periodStart":"2023-04-12","periodEnd":"2025-01-17","datasets":["JGAD000310","JGAD000371","JGAD000372","JGAD000373"]},{"principalInvestigator":{"en":"Yong-Fei WANG"},"affiliation":{"en":"Warshel Institue for Computational Biology, School of Medicine, The Chinese University of Hong Kong, Shenzhen"},"country":{"ja":"中国","en":"China"},"researchTitle":{"en":"Investigating the Molecular Mechanisms of Systemic Lupus Erythematosus Using Functional Genomics Data"},"periodStart":"2023-06-21","periodEnd":"2025-05-28","datasets":["JGAD000371","JGAD000372","JGAD000373","JGAD000603"]},{"principalInvestigator":{"ja":"久保田 晋平","en":"Shimpei Kubota"},"affiliation":{"ja":"遺伝子病制御研究所, 北海道大学","en":"Molecular Psychoneuroimmunology, Hokkaido University"},"country":{"ja":"日本","en":"Japan"},"researchTitle":{"ja":"関節リウマチおよび全身性エリテマトーデスにおける遺伝子発現および炎症増幅回路活性化因子の解析","en":"Gene expression and IL-6 amplifying circuit activators in rheumatoid arthritis and systemic lupus erythematosus"},"periodStart":"2024-02-26","periodEnd":"2026-03-31","datasets":["JGAD000309","JGAD000310","JGAD000371","JGAD000372","JGAD000373","JGAD000406","JGAD000602","JGAD000603","JGAD000727"]},{"principalInvestigator":{"ja":"ヴィセ ティモシー","en":"Timothy Vyse"},"affiliation":{"ja":"キングス・カレッジ・ロンドン, 分子遺伝学と医学遺伝学","en":"molecular and medical genetics, King's College London"},"country":{"ja":"イギリス","en":"United Kingdom"},"researchTitle":{"ja":"全身性狼瘡のシーケンスに基づく遺伝子解析","en":"Sequencing Based Genetic Analysis of Systemic Lupus"},"periodStart":"2023-08-25","periodEnd":"2025-10-16","datasets":["JGAD000603"]},{"principalInvestigator":{"ja":"鈴木 宏尚","en":"Hironao Suzuki"},"affiliation":{"ja":"新薬創生センター　薬理部, 科研製薬株式会社","en":"Pharmacology Department, Drug Research Center, Kaken Pharmaceutical,co.,LTD."},"country":{"ja":"日本","en":"Japan"},"researchTitle":{"ja":"SLE患者検体の遺伝子発現データを用いたバイオインフォマティクス解析 ","en":"Bioinformatics analysis of immune cells from SLE patients"},"periodStart":"2024-05-09","periodEnd":"2025-04-17","datasets":["JGAD000603"]},{"principalInvestigator":{"en":"Hui Li"},"affiliation":{"en":"Department of Pathology, University of Virginia"},"country":{"ja":"アメリカ合衆国","en":"United States"},"researchTitle":{"en":"Gene fusions and RNA Trans-splicing in normal and neoplastic human cells"},"periodStart":"2025-06-25","periodEnd":"2026-12-31","datasets":["JGAD000309","JGAD000310","JGAD000371","JGAD000372","JGAD000406","JGAD000603","JGAD000727","JGAD000755","JGAD000756"]},{"principalInvestigator":{"ja":"藩 龍馬","en":"Tatsuma Ban"},"affiliation":{"ja":"大学院医学研究科・免疫学教室, 横浜市立大学","en":"Department of Immunology, Graduate School of Medicine, Yokohama City University"},"country":{"ja":"日本","en":"Japan"},"researchTitle":{"ja":"免疫系転写因子群に着目した自己免疫疾患の病態解明と治療法開発","en":"Pathophysiology and therapeutic development of autoimmune diseases focusing on transcription factors of the immune system"},"periodStart":"2024-11-12","periodEnd":"2027-03-31","datasets":["JGAD000371","JGAD000372","JGAD000373","JGAD000603","JGAD000756"]},{"principalInvestigator":{"en":"Pranidhi Sood"},"affiliation":{"en":"Wield Therapeutics, Inc"},"country":{"ja":"アメリカ合衆国 (カリフォルニア州)","en":"California, United States"},"researchTitle":{"en":"Identifying Gene Expression Based Biomarkers in Patients with Autoimmune Diseases to Predict\r\nResponse to New Therapies Developed by Wield Therapeutics"},"periodStart":"2025-06-25","periodEnd":"2027-04-23","datasets":["JGAD000309","JGAD000310","JGAD000371","JGAD000372","JGAD000373","JGAD000406","JGAD000602","JGAD000603","JGAD000727","JGAD000755","JGAD000756","JGAD000778"]},{"principalInvestigator":{"ja":"松本 功","en":"Isao Matsumoto"},"affiliation":{"ja":"膠原病リウマチアレルギー内科学, 筑波大学医学医療系","en":"Department of Rheumatology, Institute of Medicine, University of 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