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Journal Article
Structural cells are key regulators of organ-specific immune responses
2020
Overview
The mammalian immune system implements a remarkably effective set of mechanisms for fighting pathogens
1
. Its main components are haematopoietic immune cells, including myeloid cells that control innate immunity, and lymphoid cells that constitute adaptive immunity
2
. However, immune functions are not unique to haematopoietic cells, and many other cell types display basic mechanisms of pathogen defence
3
–
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 38/39
/ 45
/ 45/15
/ 45/91
/ 631/114
/ 631/250
/ 631/553
/ 64/60
/ 96/21
/ 96/95
/ Animals
/ Datasets
/ Epigenesis, Genetic - immunology
/ Epithelial Cells - immunology
/ Female
/ Gene Expression Regulation - genetics
/ Gene Expression Regulation - immunology
/ Gene Regulatory Networks - genetics
/ Gene Regulatory Networks - immunology
/ Genomes
/ Hematopoietic Stem Cells - cytology
/ Hematopoietic Stem Cells - immunology
/ Humanities and Social Sciences
/ Lymphocytic Choriomeningitis - immunology
/ Lymphocytic Choriomeningitis - virology
/ Lymphocytic choriomeningitis virus - immunology
/ Male
/ Mapping
/ Mice
/ Organ Specificity - genetics
/ Organ Specificity - immunology
/ Organs
/ Science
