TY - JOUR
T1 - Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjögren's syndrome
AU - Tasaki, Shinya
AU - Suzuki, Katsuya
AU - Nishikawa, Ayumi
AU - Kassai, Yoshiaki
AU - Takiguchi, Maiko
AU - Kurisu, Rina
AU - Okuzono, Yuumi
AU - Miyazaki, Takahiro
AU - Takeshita, Masaru
AU - Yoshimoto, Keiko
AU - Yasuoka, Hidekata
AU - Yamaoka, Kunihiro
AU - Ikeura, Kazuhiro
AU - Tsunoda, Kazuyuki
AU - Morita, Rimpei
AU - Yoshimura, Akihiko
AU - Toyoshiba, Hiroyoshi
AU - Takeuchi, Tsutomu
N1 - Publisher Copyright:
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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.
AB - 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.
KW - Disease Activity
KW - Gene Polymorphism
KW - Sjgren's Syndrome
UR - https://www.scopus.com/pages/publications/85024397242
UR - https://www.scopus.com/pages/publications/85024397242#tab=citedBy
U2 - 10.1136/annrheumdis-2016-210788
DO - 10.1136/annrheumdis-2016-210788
M3 - Article
C2 - 28522454
AN - SCOPUS:85024397242
SN - 0003-4967
VL - 76
SP - 1458
EP - 1466
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
IS - 8
ER -