Krausgruber and Fortelny et al. isolated structural cells (i.e. epithelium, endothelium, and fibroblasts) from 12 mouse organs, observing cell type and organ-specific differences in expression and transcriptional regulation of immune-related genes. In homeostasis, immune interaction molecules and secreted factors were widely expressed in structural cells and varied more strongly between organs than between cell types in the same organ. Genes with low expression but high chromatin accessibility were enriched in immune interactors and indicated epigenetic potential for upregulation, confirmed in viral infection or cytokine treatment.
Contributed by Alex Najibi
ABSTRACT: 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.