Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjögren's syndrome

Shinya Tasaki, Katsuya Suzuki, Ayumi Nishikawa, Yoshiaki Kassai, Maiko Takiguchi, Rina Kurisu, Yuumi Okuzono, Takahiro Miyazaki, Masaru Takeshita, Keiko Yoshimoto, Hidekata Yasuoka, Kunihiro Yamaoka, Kazuhiro Ikeura, Kazuyuki Tsunoda, Rimpei Morita, Akihiko Yoshimura, Hiroyoshi Toyoshiba, Tsutomu Takeuchi

研究成果: Article

24 引用 (Scopus)

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Objectives Multiomics study was conducted to elucidate the crucial molecular mechanisms of primary Sjögren's syndrome (SS) pathology. Methods We generated multiple data set from well-defined patients with SS, which includes whole-blood transcriptomes, serum proteomes and peripheral immunophenotyping. Based on our newly generated data, we performed an extensive bioinformatic investigation. Results Our integrative analysis identified SS gene signatures (SGS) dysregulated in widespread omics layers, including epigenomes, mRNAs and proteins. SGS predominantly involved the interferon signature and ADAMs substrates. Besides, SGS was significantly overlapped with SS-causing genes indicated by a genome-wide association study and expression trait loci analyses. Combining the molecular signatures with immunophenotypic profiles revealed that cytotoxic CD8 T cellswere associated with SGS. Further, we observed the activation of SGS in cytotoxic CD8 T cells isolated from patients with SS. Conclusions Our multiomics investigation identified gene signatures deeply associated with SS pathology and showed the involvement of cytotoxic CD8 T cells. These integrative relations across multiple layers will facilitate our understanding of SS at the system level.

元の言語English
ページ(範囲)1458-1466
ページ数9
ジャーナルAnnals of the Rheumatic Diseases
76
発行部数8
DOI
出版物ステータスPublished - 01-08-2017

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

フィンガープリント Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjögren's syndrome' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

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    Tasaki, S., Suzuki, K., Nishikawa, A., Kassai, Y., Takiguchi, M., Kurisu, R., Okuzono, Y., Miyazaki, T., Takeshita, M., Yoshimoto, K., Yasuoka, H., Yamaoka, K., Ikeura, K., Tsunoda, K., Morita, R., Yoshimura, A., Toyoshiba, H., & Takeuchi, T. (2017). Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjögren's syndrome. Annals of the Rheumatic Diseases, 76(8), 1458-1466. https://doi.org/10.1136/annrheumdis-2016-210788