Distinct transcriptome architectures underlying lupus establishment and exacerbation

Autor: Masahiro Nakano, Mineto Ota, Yusuke Takeshima, Yukiko Iwasaki, Hiroaki Hatano, Yasuo Nagafuchi, Takahiro Itamiya, Junko Maeda, Ryochi Yoshida, Saeko Yamada, Aya Nishiwaki, Haruka Takahashi, Hideyuki Takahashi, Yuko Akutsu, Takeshi Kusuda, Hiroyuki Suetsugu, Lu Liu, Kwangwoo Kim, Xianyong Yin, So-Young Bang, Yong Cui, Hye-Soon Lee, Hirofumi Shoda, Xuejun Zhang, Sang-Cheol Bae, Chikashi Terao, Kazuhiko Yamamoto, Tomohisa Okamura, Kazuyoshi Ishigaki, Keishi Fujio
Rok vydání: 2022
Předmět:
Zdroj: Cell. 185:3375-3389.e21
ISSN: 0092-8674
Popis: Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving multiple immune cells. To elucidate SLE pathogenesis, it is essential to understand the dysregulated gene expression pattern linked to various clinical statuses with a high cellular resolution. Here, we conducted a large-scale transcriptome study with 6,386 RNA sequencing data covering 27 immune cell types from 136 SLE and 89 healthy donors. We profiled two distinct cell-type-specific transcriptomic signatures: disease-state and disease-activity signatures, reflecting disease establishment and exacerbation, respectively. We then identified candidate biological processes unique to each signature. This study suggested the clinical value of disease-activity signatures, which were associated with organ involvement and therapeutic responses. However, disease-activity signatures were less enriched around SLE risk variants than disease-state signatures, suggesting that current genetic studies may not well capture clinically vital biology. Together, we identified comprehensive gene signatures of SLE, which will provide essential foundations for future genomic and genetic studies.
Databáze: OpenAIRE