Multi-organ single-cell analysis reveals an on/off switch system with potential for personalized treatment of immunological diseases.

ABSTRACT: Prioritization of disease mechanisms, biomarkers, and drug targets in immune-mediated inflammatory diseases (IMIDs) is complicated by altered interactions between thousands of genes. Our multi-organ single-cell RNA sequencing of a mouse IMID model, namely collagen-induced arthritis, shows highly complex and heterogeneous expression changes in all analyzed organs, even though only joints showed signs of inflammation. We organized those into a multi-organ multicellular disease model, which shows predicted molecular interactions within and between organs. That model supports that inflammation is switched on or off by altered balance between pro- and anti-inflammatory upstream regulators (URs) and downstream pathways. Meta-analyses of human IMIDs show a similar, but graded, on/off switch syste

SUBMITTER: Lilja S 

PROVIDER: S-EPMC10040389 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature