The mammalian immune system implements a remarkably effective set of mechanisms for fighting pathogens. Its main components are haematopoietic immune cells, including myeloid cells that control innate immunity, and lymphoid cells that constitute adaptive immunity. However, immune functions are not unique to haematopoietic cells, and many other cell types display basic mechanisms of pathogen defence. 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 are key regulators of organ-specific immune responses.
Thomas Krausgruber* & Nikolaus Fortelny* et al.
Nature (2020), doi: 10.1038/s41586-020-2424-4

For further context, please see the following News & Views articles:

An antiviral response beyond immune cells.
Tomás Gomes & Sarah A. Teichmann
Nature (2020), doi: 10.1038/d41586-020-01916-2

A gene atlas of ‘structural immunity’.
Kirsty Minton
Nature Reviews Immunology (2020), doi: 10.1038/s41577-020-0398-y

Organ immune responses — don’t forget the structural cells.
Zewen Kelvin Tuong & Menna R. Clatworthy
Nature Reviews Nephrology (2020), doi: 10.1038/s41581-020-00334-x

Study overview

Multi-omics profiling establishes cell-type-specific and organ-specific characteristics of structural cells.

Gene expression profiles of structural cells predict cell-type-specific crosstalk.

The immunological potential of structural cells is epigenetically encoded.

Response to viral infection realizes the immunological potential of structural cells.


This section provides access to raw data and analysis results.

Description Links
Genome (mm10) browser tracks:
All samples and assays, fully customizable: UCSC Track Hub
Aggregated ATAC-seq tracks: Link
Aggregated ChIPmentation tracks: Link
Aggregated RNA-seq tracks: Link
Aggregated RNA-seq tracks of cytokine treatments: Link
Sequencing data
(Uploaded to Gene expression omnibus - GEO)
Superseries across all data (GEO SuperSeries GSE134663)
ATAC-seq data (GEO Series GSE134648)
ChIPmentation data (GEO Series GSE134658)
RNA-seq data (GEO Series GSE134659)
RNA-seq data of cytokine treatments (GEO Series GSE145820)
(Supplementary Table 1) Sequencing statistics of this dataset (XLS)
(Supplementary Table 2) Expressed marker genes (XLS)
(Supplementary Table 3) Cell-cell interactions network at homeostasis (XLS)
(Supplementary Table 4) Categorized list of immune-related receptors and ligands (XLS)
(Supplementary Table 5) Counts of structural cells in the Tabula Muris dataset (XLS)
(Supplementary Table 6) Epigenomic marker regions (XLS)
(Supplementary Table 7) Genes with epigenetic potential (XLS)
(Supplementary Table 9) Differential genes upon LCMV infection (XLS)
(Supplementary Table 8) Curated list of immune-related gene sets used for enrichment analysis (XLS)
(Supplementary Table 10) Changes in cell-cell interactions network upon LCMV infection (XLS)
(Supplementary Table 11) Differential genes upon Cytokine treatments (XLS)
All code relevant for data processing and analysis (ZIP archive)


If you use these data in your research, please cite:

Thomas Krausgruber*, Nikolaus Fortelny*, Victoria Fife-Gernedl, Martin Senekowitsch, Linda C. Schuster, Alexander Lercher, Amelie Nemc, Christian Schmidl, André F. Rendeiro, Andreas Bergthaler and Christoph Bock. Structural cells are key regulators of organ-specific immune responses. Nature (2020), doi: 10.1038/s41586-020-2424-4
* These authors contributed equally to this work

Correspondence: (C.B.)