Gene expression variability across cells and species shapes innate immunity.

Abstract:

:As the first line of defence against pathogens, cells mount an innate immune response, which varies widely from cell to cell. The response must be potent but carefully controlled to avoid self-damage. How these constraints have shaped the evolution of innate immunity remains poorly understood. Here we characterize the innate immune response's transcriptional divergence between species and variability in expression among cells. Using bulk and single-cell transcriptomics in fibroblasts and mononuclear phagocytes from different species, challenged with immune stimuli, we map the architecture of the innate immune response. Transcriptionally diverging genes, including those that encode cytokines and chemokines, vary across cells and have distinct promoter structures. Conversely, genes that are involved in the regulation of this response, such as those that encode transcription factors and kinases, are conserved between species and display low cell-to-cell variability in expression. We suggest that this expression pattern, which is observed across species and conditions, has evolved as a mechanism for fine-tuned regulation to achieve an effective but balanced response.

journal_name

Nature

journal_title

Nature

authors

Hagai T,Chen X,Miragaia RJ,Rostom R,Gomes T,Kunowska N,Henriksson J,Park JE,Proserpio V,Donati G,Bossini-Castillo L,Vieira Braga FA,Naamati G,Fletcher J,Stephenson E,Vegh P,Trynka G,Kondova I,Dennis M,Haniffa M,No

doi

10.1038/s41586-018-0657-2

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

197-202

issue

7730

eissn

0028-0836

issn

1476-4687

pii

10.1038/s41586-018-0657-2

journal_volume

563

pub_type

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