Integrated Immune Cell-Cell Communication Networks Underpinning Rheumatoid Arthritis Pathogenesis

Abstract

Rheumatoid Arthritis (RA) is a chronic, systemic auto-inflammatory disease that targets peripheral joints causing bone erosion, worsened mobility, and lower quality of life. RA is a complex autoimmune disease that develops through the combined actions of many cell types. In particular, monocytes, fibroblasts, and T cells play critical roles within the arthritic joint driving disease pathogenesis. These cells communicate with each other via ligand-receptor interactions orchestrating inflammatory responses ultimately leading to joint destruction. However, it remains unclear how the combined efforts of these different cells form an integrated network of immune responses which ultimately lead to disease development. Therefore, we hypothesized that an integrated communication network between the different immune cells found within RA joints functions to promote inflammation and drive RA disease pathogenesis. I utilized predictive assessment of cell-cell communication networks through single-cell RNA-sequencing to determine how immune cell interactions differ between autoimmune and non-autoimmune joint destruction. These studies identified a novel cell-cell communication network in which monocytes, fibroblasts and T cells cooperate to promote cell-cell interactions, immune activation, and induction of pro-inflammatory gene networks. Together, these results identify numerous potential therapeutic targets for the intervention of RA disease.