2020 Fiscal Year Final Research Report
Study of connective tissue disease-associated interstitial lung disease (CTD-ILD) with single-cell RNA sequencing
Project/Area Number |
19K24000
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0904:Internal medicine of the bio-information integration and related fields
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Research Institution | Kyoto Prefectural University of Medicine |
Principal Investigator |
Fujii Wataru 京都府立医科大学, 医学部附属病院, 専攻医 (60755643)
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Project Period (FY) |
2019-08-30 – 2021-03-31
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Keywords | 膠原病関連間質性肺疾患 / シングルセルRNA-seq / 気管支肺胞洗浄液 / 肺胞マクロファージ / 関節リウマチ / シェーグレン症候群 / 全身性強皮症 |
Outline of Final Research Achievements |
We performed single-cell RNA-seq and ELISA for bronchoalveolar lavage fluid (BALF) and peripheral blood from 5 rheumatoid arthritis (RA), 4 dermatomyositis (DM), 2 systemic sclerosis (SSc), 4 Sjogren syndrome (SjS) and 7 idiopathic interstitial pneumonia (IIP) patients. We found neutrophils increased in BALF of RA patients, while lymphocytes increased in BALF of DM and SjS patients. The concentrations of IL-12p40 and CXCL10, both are associated with lymphocyte chemotaxis, were increased in BALF of DM and SJS patients. By using scRNA-seq, we found 14 different phenotypes of alveolar macrophages in CTD-ILD patients. In conclusion, neutrophils increase in BALF of RA patients while lymphocytes increase in those of DM and SjS patients, possibly because of altered chemokine levels in BALF. Alveolar macrophages showed different phenotypes in CTD-ILD patients from those in IIP patients, indicating altered functions of these cells in CTD-ILD.
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Free Research Field |
免疫学、リウマチ学、呼吸器学
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Academic Significance and Societal Importance of the Research Achievements |
関節リウマチ、シェーグレン症候群、多発性筋炎・皮膚筋炎、全身性強皮症などの膠原病ではしばしば難治性の間質性肺疾患を合併し膠原病関連間質性肺疾患(CTD-ILD)と呼ばれるが、その分子病態は十分解明されておらず特異的治療法も確立されていない。本研究によって、CTD-ILDにおける各基礎疾患毎の分子病態の特徴が明らかとなり、病態解明および間質性肺疾患の鑑別診断のための臨床応用が期待できる。 また今回確立した気管支肺胞洗浄液と血液検体の網羅的遺伝子解析による研究手法は、CTD-ILDのみならず種々の呼吸器・免疫疾患の病態解明に適用可能であり今後の難治性呼吸器・免疫疾患研究への応用が期待できる。
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