Research Paper Volume 13, Issue 16 pp 20511—20533

A comprehensive transcriptomic analysis of alternate interferon signaling pathways in peripheral blood mononuclear cells in rheumatoid arthritis

Liang Han1, *, , Shenghao Tu1, *, , Pan Shen1, , Jiahui Yan1, , Yao Huang1, , Xin Ba1, , Tingting Li1, , Weiji Lin1, , Huihui Li2, , Kun Yu2, , Jing Guo3, , Ying Huang1, , Kai Qin1, , Yu Wang1, , Zhe Chen1, ,

  • 1 Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China
  • 2 Department of Cardiology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China
  • 3 Wuhan Institute of Biotechnology, Wuhan Biobank, Wuhan 430000, China
* Equal contribution

Received: May 18, 2021       Accepted: August 3, 2021       Published: August 25, 2021
How to Cite

Copyright: © 2021 Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Interferon (IFN) signaling pathways play crucial roles in the pathogenesis of rheumatoid arthritis (RA). Prior studies have mainly studied mixed alterations in the IFN signaling pathway in RA, but these studies have not been sufficient to elucidate how imbalanced IFN signaling subtly influences immune cells. Single-cell RNA (scRNA) sequencing makes it possible to better understand the alternations in the interferon signaling pathways in RA. In the present study, we found that IFN signaling pathways were activated in natural killer (NK) cells, monocytes, T cells, B cells, and most immune cell subclasses in RA. We then explored and analyzed the connections between abnormal IFN signaling pathways and cellular functional changes in RA. Single-Cell rEgulatory Network Inference and Clustering (SCENIC) analysis and gene regulatory network (GRN) construction were also performed to identify key transcription factors in RA. Finally, we also investigated altered IFN signaling pathways in multiple RA peripheral blood samples, which indicated that abnormal IFN signaling pathways were universally observed in RA. Our study contributes to a better understanding of the delicate and precise regulation of IFN signaling in the immune system in RA. Furthermore, common alternations in IFN signaling pathway-related transcription factors could help to identify novel therapeutic targets for RA treatment.


DCs: dendritic cells; IFNs: interferons; SLE: systemic lupus erythematosus; pSS: primary Sjögren syndrome; IL: interleukin; TNF: tumor necrosis factor; CIA: collagen-induced arthritis; scRNA: single cell RNA; PCA: principal component analysis; UMAP: uniform manifold approximation and projection; pDCs: plasmacytoid DCs; mDCs: myeloid DCs; GSEA: gene set enrichment analysis; HC: healthy control individuals; GO: Gene Ontology; BP: biological process; DEGs: differentially expressed genes; KEGG: Kyoto Encyclopedia of Genes and Genomes; SCENIC: Single-Cell rEgulatory Network Inference and Clustering; GRNs: gene regulatory networks; IFNAR: type I IFN receptor; 25HC: 25-hydroxycholesterol; Treg: regulatory T cells; anti-CCP: anti-cyclic citrullinated peptide; RF: rheumatoid factor; GEO: Gene Expression Omnibus; fRMA: frozen Robust Multi-array Analysis; CCA: canonical correlation analysis; KNN: K-nearest neighbors; NES: normalized enrichment score; BH: Benjamini–Hochberg.