Leveraging Multi-Tissue, Single-Cell Atlases as Tools to Elucidate Shared Mechanisms of Immune-Mediated Inflammatory Diseases

Abstract

The observation that certain therapeutic strategies for targeting inflammation benefit patients with distinct immune-mediated inflammatory diseases (IMIDs) is exemplified by the success of TNF blockade in conditions including rheumatoid arthritis, ulcerative colitis, and skin psoriasis, albeit only for subsets of individuals with each condition. This suggests intersecting “nodes” in inflammatory networks at a molecular and cellular level may drive and/or maintain IMIDs, being “shared” between traditionally distinct diagnoses without mapping neatly to a single clinical phenotype. In line with this proposition, integrative tumour tissue analyses in oncology have highlighted novel cell states acting across diverse cancers, with important implications for precision medicine. Drawing upon advances in the oncology field, this narrative review will first summarise learnings from the Human Cell Atlas in health as a platform for interrogating IMID tissues. It will then review cross-disease studies to date that inform this endeavour before considering future directions in the field.

Keywords

• immune-mediated inflammatory diseases
• single-cell sequencing
• multi-tissue atlas
• cross-tissue atlas
• human cell atlas
• integrative analysis