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

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1458-1466
Number of pages9
JournalAnnals of the Rheumatic Diseases
Volume76
Issue number8
DOIs
Publication statusPublished - 2017 Aug 1

    Fingerprint

Keywords

  • Disease Activity
  • Gene Polymorphism
  • Sjgren's Syndrome

ASJC Scopus subject areas

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

Cite this

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