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Transcriptional profiling unveils type I and II interferon networks in blood and tissues across diseases

Research output: Contribution to journalArticle

Akul Singhania, Christine Graham, Leona Gabrysova, Lucia Moreira-Teixeira, Evangelos Stavropoulos, Jonathan Pitt, Probir Chakravarty, Annika Warnatsch, William Branchett, Laura Conejero, Jing-Wen Lin, Sophia Davidson, Mark Wilson, Gregory Bancroft, Jean Langhorne, Eva Frickel, Abdul Sesay, Simon Priestnall, Eleanor Herbert, Marianna Ioannou & 15 others Qian Wang, Ian Humphreys, Jonathan Dodd, Peter Openshaw, Katrin Mayer-Barber, Dragana Jankovic, Alan Sher, Clare Lloyd, Nicole Baldwin, Damien Chaussabel, Venizelos Papayannopoulos, Andreas Wack, Jacques Banchereau, Virginia Pascual, Anne O'Garra

Original languageEnglish
Article number2887
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

King's Authors

Abstract

Understanding how immune challenges elicit different responses is critical for diagnosing and deciphering immune regulation. Using a modular strategy to interpret the complex transcriptional host response in mouse models of infection and inflammation, we show a breadth of immune responses in the lung. Lung immune signatures are dominated by either IFN-γ and IFN-inducible, IL-17-induced neutrophil- or allergy-associated gene expression. Type I IFN and IFN-γ-inducible, but not IL-17- or allergy-associated signatures, are preserved in the blood. While IL-17-associated genes identified in lung are detected in blood, the allergy signature is only detectable in blood CD4+ effector cells. Type I IFN-inducible genes are abrogated in the absence of IFN-γ signaling and decrease in the absence of IFNAR signaling, both independently contributing to the regulation of granulocyte responses and pathology during Toxoplasma gondii infection. Our framework provides an ideal tool for comparative analyses of transcriptional signatures contributing to protection or pathogenesis in disease.

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