Dynamic landscape of immune cell-specific gene regulation in immune-mediated diseases

Mineto Ota, Yasuo Nagafuchi, Hiroaki Hatano, Kazuyoshi Ishigaki, Chikashi Terao, Yusuke Takeshima, Haruyuki Yanaoka, Satomi Kobayashi, Mai Okubo, Harumi Shirai, Yusuke Sugimori, Junko Maeda, Masahiro Nakano, Saeko Yamada, Ryochi Yoshida, Haruka Tsuchiya, Yumi Tsuchida, Shuji Akizuki, Hajime Yoshifuji, Koichiro OhmuraTsuneyo Mimori, Ken Yoshida, Daitaro Kurosaka, Masato Okada, Keigo Setoguchi, Hiroshi Kaneko, Nobuhiro Ban, Nami Yabuki, Kosuke Matsuki, Hironori Mutoh, Sohei Oyama, Makoto Okazaki, Hiroyuki Tsunoda, Yukiko Iwasaki, Shuji Sumitomo, Hirofumi Shoda, Yuta Kochi, Yukinori Okada, Kazuhiko Yamamoto, Tomohisa Okamura, Keishi Fujio

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Genetic studies have revealed many variant loci that are associated with immune-mediated diseases. To elucidate the disease pathogenesis, it is essential to understand the function of these variants, especially under disease-associated conditions. Here, we performed a large-scale immune cell gene-expression analysis, together with whole-genome sequence analysis. Our dataset consists of 28 distinct immune cell subsets from 337 patients diagnosed with 10 categories of immune-mediated diseases and 79 healthy volunteers. Our dataset captured distinctive gene-expression profiles across immune cell types and diseases. Expression quantitative trait loci (eQTL) analysis revealed dynamic variations of eQTL effects in the context of immunological conditions, as well as cell types. These cell-type-specific and context-dependent eQTLs showed significant enrichment in immune disease-associated genetic variants, and they implicated the disease-relevant cell types, genes, and environment. This atlas deepens our understanding of the immunogenetic functions of disease-associated variants under in vivo disease conditions.

Original languageEnglish
Pages (from-to)3006-3021.e17
JournalCell
Volume184
Issue number11
DOIs
StatePublished - 27 May 2021
Externally publishedYes

Keywords

  • Immune Cell Gene Expression Atlas from the University of Tokyo
  • cell-type-specific eQTL
  • context-dependent eQTL
  • expression quantitative trait loci
  • gene regulation
  • immune cell
  • immune-mediated disease
  • immunogenetics
  • systemic lupus erythematosus
  • transcriptome

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