{"id":"hum0443","version":1,"url":"https://humandbs.dbcls.jp/research/hum0443/v1","datePublished":"2024-05-10","versions":[{"version":1,"datePublished":"2024-05-10"}],"title":{"ja":"妊娠前後での制御性T細胞のT細胞受容体レパートリーの変化と妊娠予後との関係","en":"Relationship between changes in the T-cell receptor repertoire of regulatory T cells before and after pregnancy and pregnancy outcome."},"summary":{"aims":{"ja":"胎児は母体にとって異物である父親由来抗原を発現するが、妊娠中は母子間免疫寛容が成立しているため拒絶されない。一方で、妊娠中でも外来微生物に対する免疫応答は維持されている。母子境界領域での、免疫応答を抑制する制御性T細胞（Treg）と、炎症反応に寄与するCD4陽性T細胞・細胞障害性T細胞との適切なバランスが妊娠維持に重要である。しかし、母子境界面（脱落膜）における多様なCD4陽性細胞とTregの全体像ならびに、妊娠高血圧腎症（PE）における変化は明らかになっていない。そこで、脱落膜CD4陽性T細胞ならびにTregの単一細胞mRNA解析+T細胞受容体（TCR）解析を行い、正常妊娠におけるCD4陽性細胞とTregの多様性を明らかにするとともに、PEの病態関連分子を明らかにすることを目的とした。","en":"A fetus expresses paternally derived antigens which is allogenic for a mother, however; fetus is not rejected from maternal immune cells because of feto-maternal immune tolerance during pregnancy. At the same time, maternal immune system still maintains their ability to respond against pathogenic organisms. The adequate balance between tolerogenic regulatory T cells (Treg) and proinflammatory CD4+ T cells and cytotoxic T cells at feto-maternal interface is important for healthy pregnancies. However, diversity of CD4+ T cells and Tregs in healthy pregnancies and its alternation in preeclampsia (PE) have not been fully understood. Therefore, we conducted single-cell mRNA sequencing and T cell receptor repertoire analysis to reveal a landscape of diverse CD4 T cells and Treg in healthy pregnancies and altered gene expression patterns which relate to pathogenesis of PE."},"methods":{"ja":"脱落膜・末梢血からリンパ球を分離し、セルソーターでCD4+T細胞を分取した。これらをBD Rhapsody Single-Cell Analysis Systemにロードし、targeted RNA sequece用ならびにTCRsequence用cDNAライブラリーを作製後、シークエンスを実施した。","en":"Lymphocytes were isolated from decidual tissue and peripheral blood. CD4+ T cells were sorted and subjected into BD Rhapsody Single-Cell Analysis System. Targeted RNA-sequence and TCR sequence libraries were constructed. Sequencing was performed using Illumina NovaSeq 6000."},"targets":{"ja":"targeted RNA-seq：正常妊娠初期脱落膜CD4+T細胞4例、正常妊娠後期脱落膜CD4+T細胞3例、妊娠高血圧腎症脱落膜CD4+T細胞3例、 正常妊娠後期末梢血CD4+T細胞1例（正常妊娠後期脱落膜1例と同じ対象由来）\nTCR-seq：正常妊娠初期脱落膜2例、正常妊娠後期脱落膜1例、正常妊娠後期末梢血1例、妊娠高血圧腎症脱落膜1例","en":"Healthy early pregnancy decidual CD4+ T cells (n=4), Healthy late pregnancy decidual CD4+ T cells (n=3), Preeclampsia decidual CD4+ T cells (n=3), Healthy late pregnancy peripheral blood CD4+ T cells (n=1) . One pairs of healthy late decidua and peripheral blood was from the same subject. All samples were subjected to targeted RNA-sequencing with the BD Rhapsody. TCR-sequence was performed in 2 healthy early, 1 healthy late decidua, 1 healthy late peripheral blood, and 1 preeclampsia decidua."},"url":{"ja":null,"en":null}},"listingSummary":{"methods":{"ja":"発現","en":"Expression profiling"},"targets":{"ja":"正常妊娠：7名\n妊娠高血圧腎症：3症例\n（日本人）","en":"Healthy pregnancy: 7 subjects\nPreeclampsia: 3 cases\n(Japanese)"},"typeOfData":{"ja":"NGS\n（Target RNA-seq、TCR-seq）","en":"NGS\n(Target RNA-seq, TCR-seq)"}},"releaseNote":{"ja":"正常妊娠7名（初期4名、後期3名）および妊娠高血圧腎症3例の脱落膜・末梢血より分取したCD4+T細胞から抽出したRNAを用いたTarget RNA-seq解析ならびにTCR-seq解析結果をfastqファイル形式で提供する。","en":"RNAs extracted from CD4+ T cells isolated from decidual tissue and peripheral blood from healthy early pregnancy, healthy late pregnancy and patients with preeclampsia were used for the Target RNA sequencing and TCR sequencing analyses. Fastq files are provided."},"dataProviders":[{"name":{"ja":"中島 彰俊","en":"Akitoshi Nakashima"},"organization":{"name":{"ja":"富山大学 学術研究部医学系 産科婦人科学教室","en":"Department of Obstetrics and Gynecology, University of Toyama"}}}],"researchProjects":[],"grants":[{"title":{"ja":"父親抗原特異的制御性T細胞と樹状細胞による母児免疫寛容誘導メカニズムの解明","en":"The crosstalk of paternal antigen specific Treg cells and dendritic cells in feto-maternal tolerance"},"agency":{"ja":"科学研究費助成事業 基盤研究（C）","en":"KAKENHI Grant-in-Aid for Scientific Research (C)"},"grantIds":["17K11221"]},{"title":{"ja":"T細胞受容体レパートリーの観点から見た妊娠と子宮悪性腫瘍の免疫学的相違","en":"Immunological differece between pregnancy and cancer in terms of T cell receptor repertoire."},"agency":{"ja":"科学研究費助成事業 若手研究","en":"KAKENHI Grant-in-Aid for Early-Career Scientists"},"grantIds":["19K18690"]},{"title":{"ja":"単一T細胞トランスクリプトーム解析による妊娠高血圧腎症治療のバイオマーカー探索","en":"Single T cell transcriptome analysis for biomarker discovery in the treatment of preeclampsia."},"agency":{"ja":"科学研究費助成事業 若手研究","en":"KAKENHI Grant-in-Aid for Early-Career Scientists"},"grantIds":["21K16764"]},{"title":{"ja":"妊娠高血圧腎症の病態形成機構におけるCD4陽性細胞と絨毛細胞の細胞間相互作用の解明","en":"Elucidation of pathogenesis mechanisms of preeclampsia focusing on cell-cell interaction between maternal CD4 positive T cells and trophoblasts."},"agency":{"ja":"科学研究費助成事業 国際共同研究加速基金（国際共同研究強化（A））","en":"KAKENHI Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))"},"grantIds":["22KK0287"]},{"title":{"ja":"妊娠高血圧腎症解明から見えた新規オートファジー抑制機構の解明,治療法の開発","en":"New mechanism of autophagy inhibition from the study of preeclampsia"},"agency":{"ja":"科学研究費助成事業 基盤研究（C）","en":"KAKENHI Grant-in-Aid for Scientific Research (C)"},"grantIds":["19K09750"]},{"title":{"ja":"オートファジー機能低下による妊娠高血圧症候群～治療開発およびその起源の追究～","en":"Failure of autophagy for the therapeutic target of preeclampsia"},"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":["22H03223"]},{"title":{"ja":"不育症の原因解明、予防治療に関する研究","en":"Research on elucidation of causes and preventive treatment of recurrent pregnancy loss"},"agency":{"ja":"日本医療研究開発機構（AMED） 成育疾患克服等総合研究事業","en":"Project for Baby and Infant Research of Health and Development to Adolescent and Young adult, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP18gk0110018"]}],"relatedPublications":[{"title":"CD4+ T cell heterogeneity in gestational age and preeclampsia using single-cell RNA sequencing","doi":"https://doi.org/10.3389/fimmu.2024.1401738","datasets":["DRA017833","E-GEAD-674"]}],"datasets":["DRA017833","E-GEAD-674"],"controlledAccessUsers":[]}