Toggle Main Menu Toggle Search

Open Access padlockePrints

Gene expression variability across cells and species shapes innate immunity.

Lookup NU author(s): James Fletcher, Emily Stephenson, Dr Peter Vegh, Professor Muzlifah Haniffa

Downloads


Licence

This is the authors' accepted manuscript of an article that has been published in its final definitive form by Nature Publishing Group, 2018.

For re-use rights please refer to the publisher's terms and conditions.


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.


Publication metadata

Author(s): 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, Nourmohammad A, Lässig M, Teichmann SA

Publication type: Article

Publication status: Published

Journal: Nature

Year: 2018

Volume: 563

Issue: 7730

Pages: 197-202

Print publication date: 08/11/2018

Online publication date: 24/10/2018

Acceptance date: 17/08/2018

ISSN (print): 0028-0836

ISSN (electronic): 1476-4687

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/s41586-018-0657-2

DOI: 10.1038/s41586-018-0657-2


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share