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

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journal contribution
posted on 09.01.2020 by Akul Singhania, Christine M Graham, Leona Gabryšová, Lúcia Moreira-Teixeira, Evangelos Stavropoulos, Jonathan M Pitt, Probir Chakravarty, Annika Warnatsch, William J Branchett, Laura Conejero, Jing-Wen Lin, Sophia Davidson, Mark S Wilson, Gregory Bancroft, Jean Langhorne, Eva Frickel, Abdul K Sesay, Simon L Priestnall, Eleanor Herbert, Marianna Ioannou, Qian Wang, Ian R Humphreys, Jonathan Dodd, Peter JM Openshaw, Katrin D Mayer-Barber, Dragana Jankovic, Alan Sher, Clare M Lloyd, Nicole Baldwin, Damien Chaussabel, Venizelos Papayannopoulos, Andreas Wack, Jacques F Banchereau, Virginia M Pascual, Anne O'Garra
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.

Funding

Crick (Grant ID: 10126, Grant title: O' Garra FC001126) Crick (Grant ID: 10101, Grant title: Langhorne FC001101) Crick (Grant ID: 10206, Grant title: Wack FC001206) Crick (Grant ID: 10076, Grant title: Frickel FC001076) Crick (Grant ID: 10129, Grant title: Papayannopoulos FC001129)

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