Abstract
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.
Highlights
Rheumatoid arthritis (RA) is a systemic, chronic, incurable autoimmune inflammatory disease affecting approximately 0.5%-1% of the world population [1]
Four primary immune cell classes were identified by Single-cell RNA (scRNA) transcriptome analysis To comprehensively explore the disorders in peripheral blood mononuclear cells (PBMCs) from RA, scRNA sequencing data were preprocessed, and batch effects were removed (Supplementary Figure 1A–1D)
The type I IFN signature represents type I IFN response genes and pathways, that are activated in RA patients, which may play a role in the potential development of RA [11]
Summary
Rheumatoid arthritis (RA) is a systemic, chronic, incurable autoimmune inflammatory disease affecting approximately 0.5%-1% of the world population [1]. Imbalanced immune responses both in circulating peripheral blood and in diseased joint cavities are closely related to the occurrence and development of RA [2]. As important immunomodulators, IFNs www.aging-us.com impressively affect several immunity responses [10] Both abnormal levels of IFNs and alterations in IFN signaling pathways have been observed in RA, systemic lupus erythematosus (SLE), primary Sjögren syndrome (pSS), and other autoimmune diseases [11,12,13]. The specific mechanisms of IFN signaling pathways in RA are poorly understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
