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

Annals of the Rheumatic Diseases
Shinya TasakiTsutomu Takeuchi

Abstract

Multiomics study was conducted to elucidate the crucial molecular mechanisms of primary Sjögren's syndrome (SS) pathology. 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. 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 cells- were associated with SGS. Further, we observed the activation of SGS in cytotoxic CD8 T cells isolated from patients with SS. 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.

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Citations

Mar 8, 2018·The New England Journal of Medicine·Xavier Mariette, Lindsey A Criswell
Aug 8, 2017·Science Immunology·Takeshi NittaHiroshi Takayanagi
Sep 17, 2017·Annals of the Rheumatic Diseases·Shu-Fang Wang-RenaultJörg Tost
Dec 6, 2018·Scandinavian Journal of Rheumatology·T WatanabeM Machida
Feb 17, 2019·Rheumatology·Gwenny M VerstappenHendrika Bootsma
Jan 25, 2018·Nature Reviews. Rheumatology·Guillermo BarturenMarta E Alarcón-Riquelme
Sep 10, 2019·Rheumatology·Judith A JamesE William St Clair
May 10, 2019·Frontiers in Immunology·Zhenwei LiuXiaobing Wang
May 12, 2020·Clinical Reviews in Allergy & Immunology·Yuan YaoZhe-Xiong Lian
Jul 18, 2018·Nature Communications·Shinya TasakiTsutomu Takeuchi
Mar 7, 2019·Nature Reviews. Rheumatology·Steven A Greenberg
Aug 1, 2020·European Journal of Immunology·Sandra WoyciechowskiHanspeter Pircher
Mar 14, 2020·Journal of the American Society of Nephrology : JASN·Lola JacquemontNicolas Degauque
Sep 26, 2020·Journal of Clinical Medicine·Richard WitasCuong Q Nguyen
Aug 17, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michelle MironDonna L Farber
Feb 16, 2021·Frontiers in Immunology·Huimin ZhouShengjun Wang
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Jan 15, 2021·International Journal of Molecular Sciences·Clara ChivassoMuhammad Shahnawaz Soyfoo
Mar 13, 2021·Frontiers in Immunology·Guillaume PadernYves-Marie Pers
Dec 12, 2017·Best Practice & Research. Clinical Rheumatology·Guillermo Barturen, Marta E Alarcón-Riquelme
Nov 4, 2021·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Bin WangGuixiu Shi

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Methods Mentioned

BETA
FACS

Software Mentioned

limma
Gene Set Variation Analysis ( GSVA )
SOMAmer
limma R package

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