Structural cells are key regulators of organ-specific immune response

By Thomas Krausgruber, N. Fortelny, Victoria Fife-Gernedl, M. Senekowitsch, L. Schuster, A. Lercher, A. Nemc, Christian Schmidl, André F. Rendeiro, A. Bergthaler and 1 more. Nature, 2020

381 citations recorded by the source corpus.

The mammalian immune system implements a remarkably effective set of mechanisms for fighting pathogens1. Its main components are haematopoietic immune cells, including myeloid cells that control innate immunity, and lymphoid cells that constitute adaptive immunity2. However, immune functions are not unique to haematopoietic cells, and many other cell types display basic mechanisms of pathogen defence3–5. To advance our understanding of immunology outside the haematopoietic system, here we systematically investigate the regulation of immune genes in the three major types of structural cells: epithelium, endothelium and fibroblasts. We characterize these cell types across twelve organs in mice, using cellular phenotyping, transcriptome sequencing, chromatin accessibility profiling and epigenome mapping. This comprehensive dataset revealed complex immune gene activity and regulation in structural cells. The observed patterns were highly organ-specific and seem to modulate the extensive interactions between structural cells and haematopoietic immune cells. Moreover, we identified an epigenetically encoded immune potential in structural cells under tissue homeostasis, which was triggered in response to systemic viral infection. This study highlights the prevalence and organ-specific complexity of immune gene activity in non-haematopoietic structural cells, and it provides a high-resolution, multi-omics atlas of the epigenetic and transcriptional networks that regulate structural cells in the mouse. Structural cells implement a broad range of immune-regulatory functions beyond their roles as barriers and connective tissues, and they utilize an epigenetically encoded potential for immune gene activation in their rapid response to viral infection.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/fa9e61acc18c1bab6a4dd7d909097c9b875eb4ac

Citations in the corpus

• Single-cell landscape of peripheral and tumor-infiltrating immune cells in HPV-negative HNSCC (2025, unknown): “40,41,58 Three gene sets showed broad enrichment across populations.”
• The Single-Cell Landscape of Peripheral and Tumor-infiltrating Immune Cells in HPV- HNSCC (2025, unknown): “40–42 Among the gene sets evaluated, three of them were those that showed enrichment across a wide variety of cell populations.”